What changed in this filing

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Item 1. Business

2021-03-09 compared with 2020-03-17 · 1061 added, 982 removed, 527 unchanged (79% of the section changed)

On February 26, 2020, our board of directors

determined to advance the preclinical development of our pan-RAS inhibitor program while seeking to identify financing and strategic

opportunities for the company.

The opportunities may include, but are not limited to, a licensing or collaboration agreement involving

the pan-RAS inhibitor program and/or our other in-licensed compound, a potential monetization transaction that may involve the

sale of our rights in the in-licensed compounds or a merger or other strategic transaction.

Additionally,

the assessment of strategic opportunities and the evaluation of such assessment to the extent made by our current board of directors

will be subject to review and possible change after our annual general meeting of shareholders by the then newly composed board

of directors.

On December 14, 2020, we entered

into an Agreement and Plan of Merger “(Merger Agreement”) with Chemomab Ltd.

(“Chemomab”), an Israeli

limited company and a clinical-stage biotech company focusing on the discovery and development of innovative therapeutics for

fibrosis-related diseases with high unmet need, which included the proposed business combination (“Merger”) of CMB

Acquisition Ltd., a wholly owned subsidiary of ours, with Chemomab as the surviving company, subject to shareholder approval.

As a result, you should not place undue reliance on the plans discussed below relating to the pan-RAS and PDE10/ß-catenin

programs as they are subject to change.

The merger is described in detail in a

proxy statement / prospectus that we filed with the SEC on February 12, 2021 and that is available at this link:

https://www.sec.gov/Archives/edgar/data/1534248/000110465921021553/tm211883-6_424b3.htm

We are a preclinical biotechnology company

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patients whose cancers are caused by mutated genes and for whom existing therapies are limited in effectiveness.

The first of these

technologies comprises small molecules that potently inhibit the products of RAS oncogenes.

these technologies comprises small molecules that potently inhibit the products of RAS oncogenes.

RAS oncogenes are the most frequently

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carry mutations in the Wnt/APC/β-catenin pathway genes.

Previously we discovered and developed a

gene therapy, inodiftagene vixteplasmid (“inodiftagene”), designed to treat early stage bladder cancer.

Previously we discovered and developed

a gene therapy, inodiftagene vixteplasmid (“inodiftagene”), designed to treat early stage bladder cancer.

this gene therapy in six clinical trials in pancreatic cancer, ovarian cancer, and bladder cancer.

Based on these preliminary clinical

studies, we planned and initiated a clinical trial designed as the basis for potential regulatory approval of inodiftagene.

clinical trial, the Phase 2 Codex trial, was initiated in December 2018, enrolling patients through the following year.

We terminated

the program in November 2019 based on our assessment that the observed preliminary efficacy of inodiftagene in bladder cancer was

insufficient to support regulatory approval.

Based on these preliminary

clinical studies, we planned and initiated a clinical trial designed as the basis for potential regulatory approval of inodiftagene.

This clinical trial, the Phase 2 Codex trial, was initiated in December 2018, enrolling patients through the following year.

We terminated the program in November 2019 based on our assessment that the observed preliminary efficacy of inodiftagene

in bladder cancer was insufficient to support regulatory approval.

In parallel to the now-terminated inodiftagene

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anti-cancer therapeutics.

In September 2019, we entered into a collaboration and license agreement (the “Collaboration Agreement”)

with ADT Pharmaceuticals, LLC (“ADT”) pursuant to which we agreed to use commercially reasonable efforts to conduct

research and development activities with respect to the pan-RAS and PDE10/β-catenin programs under the oversight of a jointly

established steering committee.

In addition, ADT granted us an exclusive option to license its small molecule technologies.

Collaboration Agreement covers two proprietary classes of molecules:

(1) inhibitors of RAS, and (2) inhibitors of the Wnt/APC/β-catenin

pathway via PDE10.

Pursuant to the Collaboration Agreement, we have an exclusive option to license the suite of intellectual property

covering these molecules, with granted patents that extend to 2034.

We believe we will be able to develop these molecules into

product candidates to provide new therapies for patients with cancers whose pathogenesis depends on mutant RAS oncogenes, or on

mutations in the Wnt/APC/β-catenin pathway.

Both of these genetic lesions cause enormous human suffering by reason of the

cancers they cause.

These genes are primarily responsible for lung, colorectal, and pancreatic cancers, the most common lethal

cancers, among others.

Mutations in one of the RAS genes are present in more than 30% of all human cancers, making these the most

frequent oncogenic mutations in cancer.

The Wnt/APC/β-catenin pathway genes are mutated in approximately 90% of colorectal

In September 2019, we entered into a collaboration and license agreement (the “Collaboration

Agreement”) with ADT Pharmaceuticals, LLC (“ADT”) pursuant to which we agreed to use commercially reasonable

efforts to conduct research and development activities with respect to the pan-RAS and PDE10/β-catenin programs under the

oversight of a jointly established steering committee.

In addition, ADT granted us an exclusive option to license its small molecule

technologies.

The Collaboration Agreement covers two proprietary classes of molecules:

(1) inhibitors of RAS, and (2) inhibitors

of the Wnt/APC/β-catenin pathway via PDE10.

Pursuant to the Collaboration Agreement, we have an exclusive option to license

the suite of intellectual property covering these molecules, with granted patents that extend to 2034.

We believe we will be able to develop these

molecules into product candidates to provide new therapies for patients with cancers whose pathogenesis depends on mutant RAS

oncogenes, or on mutations in the Wnt/APC/β-catenin pathway.

Both of these genetic lesions cause enormous human suffering

by reason of the cancers they cause.

These genes are primarily responsible for lung, colorectal, and pancreatic cancers, the most

common lethal cancers, among others.

Mutations in one of the RAS genes are present in more than 30% of all human cancers, making

these the most frequent oncogenic mutations in cancer.

The Wnt/APC/β-catenin pathway genes are mutated in approximately 90%

of colorectal cancers.

The impact of RAS and Wnt/APC/β-catenin

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KRAS, HRAS, and NRAS.

Of the most frequently lethal cancer types, lung cancers (non-small cell lung cancers, “NSCLC”)

have mutations in one of the RAS family of genes in approximately 35% of cases;

colorectal cancers carry RAS mutation in approximately

45% of cases;

Of the most frequently lethal cancer types, lung cancers (non-small cell lung cancers,

“NSCLC”) have mutations in one of the RAS family of genes in approximately 35% of cases;

colorectal cancers carry

RAS mutation in approximately 45% of cases;

and pancreatic cancers carry RAS mutations in over 95% of cases.

We estimate that the total addressable population

of patients with RAS-mutation driven solid tumors alone is more than 165,000 patients per year in the US.

This enormous toll of

cancer morbidity and mortality suggests that therapies directed at tumors carrying mutated forms of RAS are urgently needed.

We estimate that

the total addressable population of patients with RAS-mutation driven solid tumors alone is more than 165,000 patients per year

This enormous toll of cancer morbidity and mortality suggests that therapies directed at tumors carrying mutated forms

of RAS are urgently needed.

Treating cancers that carry mutated oncogenes

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cancer treatment paradigms that exists.

Approved small molecule targeted drugs include inhibitors of the oncogenic breakpoint cluster

region-Abelson murine leukemia viral oncogene homolog 1 (“BCR-ABL”) including imatinib, dasatinib, and ponatinib in

Approved small molecule targeted drugs include inhibitors of the oncogenic breakpoint

cluster region-Abelson murine leukemia viral oncogene homolog 1 (“BCR-ABL”) including imatinib, dasatinib, and ponatinib

inhibitors of oncogenically mutated epidermal growth factor receptor (“EGFR”) in NSCLC including erlotinib

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Until very recently,

the unique biochemistry and biology of the RAS family had resisted efforts of cancer biologists to discover and develop drugs capable

of inhibiting the activity of the mutated protein.

However, in 2014 work by Shokat and others led to new approaches to the discovery

of small molecules capable of inhibiting a particular mutated form of RAS, known as KRAS G12C.

This designates a mutation in the

KRAS member of the RAS family, in which an amino acid at position 12 is altered due to a mutation in the encoding gene.

this work led to the first demonstration in the clinic of anti-tumor response associated with treatment with KRAS G12C inhibitors

under development by Amgen and Mirati Therapeutics.

We believe the significance of these successes is field-altering, as for the

first time there is evidence that inhibition of mutated RAS isoforms may be undertaken in the same manner as other successful small

molecule targeted therapies had shown possible against other mutated oncogenes.

In other words, RAS has become a clinically validated

However, KRAS is only one of three mutated isoforms of the RAS family, and only approximately 11% of KRAS mutations are

of the G12C type.

This means that while these observations have proven that RAS-directed therapy using small molecule inhibitors

is possible with clinical effect, results so far are confined to a small subset of patients carrying a particular mutation.

said, the values of the companies pursuing KRAS G12C inhibitors has grown by many billions of dollars during 2019.

Our lead focus is our pan-RAS program, which

we believe is poised to take advantage both of the fact that RAS inhibition has been shown to be clinically valid, and initial

the unique biochemistry and biology of the RAS family had resisted efforts of cancer biologists to discover and develop drugs

capable of inhibiting the activity of the mutated protein.

However, in 2014 work by Shokat and others led to new approaches to

the discovery of small molecules capable of inhibiting a particular mutated form of RAS, known as KRAS G12C.

This designates a

mutation in the KRAS member of the RAS family, in which an amino acid at position 12 is altered due to a mutation in the encoding

In 2019, this work led to the first demonstration in the clinic of anti-tumor response associated with treatment with KRAS

G12C inhibitors under development by Amgen and Mirati Therapeutics.

We believe the significance of these successes is field-altering,

as for the first time there is evidence that inhibition of mutated RAS isoforms may be undertaken in the same manner as other

successful small molecule targeted therapies had shown possible against other mutated oncogenes.

In other words, RAS has become

a clinically validated target.

However, KRAS is only one of three mutated isoforms of the RAS family, and only approximately 11%

of KRAS mutations are of the G12C type.

This means that while these observations have proven that RAS-directed therapy using small

molecule inhibitors is possible with clinical effect, results so far are confined to a small subset of patients carrying a particular

That said, the values of the companies pursuing KRAS G12C inhibitors has grown by many billions of dollars during 2019.

Our lead focus is our pan-RAS program,

which we believe is poised to take advantage both of the fact that RAS inhibition has been shown to be clinically valid, and initial

successes by existing therapies have been confined to a fraction of tumors that carry RAS mutations.

A broadly-acting pan-RAS inhibitor

with the potential to treat RAS-driven cancers regardless of RAS isoform or mutation would be clinically useful.

We believe our

RAS-inhibitor molecules have potential for RAS inhibition in a broad variety of clinical settings.

A broadly-acting pan-RAS

inhibitor with the potential to treat RAS-driven cancers regardless of RAS isoform or mutation would be clinically useful.

believe our RAS-inhibitor molecules have potential for RAS inhibition in a broad variety of clinical settings.

The characteristics one would need in such

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These compounds inhibit downstream

signaling through RAF and PI3K pathways, which is consistent with their acting directly on RAS, as opposed to another pathway molecule.

signaling through RAF and PI3K pathways, which is consistent with their acting directly on RAS, as opposed to another pathway

They initiate cell-cycle arrest and induce apoptosis, consistent with cell killing.

Importantly, the inhibitors demonstrate blockade

of GTP loading of RAS in the nucleotide-free state in cell-free biochemical assays, suggesting that their mechanism of action is

through interference of GTP-mediated signaling.

Importantly, the inhibitors demonstrate

blockade of GTP loading of RAS in the nucleotide-free state in cell-free biochemical assays, suggesting that their mechanism of

action is through interference of GTP-mediated signaling.

They have exhibited in vivo activity in RAS-mutant tumor models.

an emerging characteristic of RAS inhibition is the stimulation of anti-tumor immunity.

This has been shown with AMG 510, a KRAS

G12C inhibitor presently in the clinic, and it suggests that effective RAS inhibition stimulates several anti-tumor immune mechanisms.

Our inhibitors have been shown to similarly stimulate anti-tumor T-cell-mediated immune mechanisms, suggesting that their mechanism

is indeed effected through RAS.

We have identified lead compounds with the

desired biologic and biochemical characteristics with regard to effecting pan-RAS inhibition.

We are undertaking additional structural

studies and medicinal chemistry to identify a clinical lead compound.

We anticipate that we will identify a clinical development

lead compound in the next 12 to18 months, followed by 12 months of Investigational New Drug (“IND”) application-enabling

Finally, an emerging characteristic of RAS inhibition is the stimulation of anti-tumor immunity.

This has been shown with AMG

510, a KRAS G12C inhibitor presently in the clinic, and it suggests that effective RAS inhibition stimulates several anti-tumor

immune mechanisms.

Our inhibitors have been shown to similarly stimulate anti-tumor T-cell-mediated immune mechanisms, suggesting

that their mechanism is indeed effected through RAS.

We have identified lead compounds with

the desired biologic and biochemical characteristics with regard to effecting pan-RAS inhibition.

We are undertaking additional

structural studies and medicinal chemistry to identify a clinical lead compound.

We anticipate that we will identify a clinical

development lead compound in the next 12 to18 months, followed by 12 months of Investigational New Drug (“IND”) application-enabling

We believe this will allow us to initiate our first in human trial in 2022.

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with RAS mutations and advanced solid tumors.

The clinical development of other targeted therapies in tumors with genetically defined

driver mutations, including the development plans for the KRAS G12C inhibitors presently under investigation, suggests that there

is a path to accelerated approval based on a single well-designed multi-center single-arm study.

We would then pursue the expansion

of indications to additional tumor types, earlier lines of therapy, and combination studies, with additional trials.

The clinical development of other targeted therapies in tumors with genetically

defined driver mutations, including the development plans for the KRAS G12C inhibitors presently under investigation, suggests

that there is a path to accelerated approval based on a single well-designed multi-center single-arm study.

We would then pursue

the expansion of indications to additional tumor types, earlier lines of therapy, and combination studies, with additional trials.

Our focus initially will be on the pan-RAS-inhibitor

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Initial plans for continued preclinical development of the

PDE10/β-catenin program will be funded by ADT using Small Business Innovation Research (“SBIR”) grants to ADT.

Our management has extensive experience

in the development and global approval of small molecule targeted therapies in their previous roles.

As such, we believe we are

positioned for the successful development of small molecule inhibitors.

We believe that our pan-RAS and PDE10/β-catenin programs

have substantial promise to lead to new development candidates with the potential to treat lethal tumors harboring RAS and Wnt/APC/β-catenin

pathway mutations in the United States and globally.

PDE10/β-catenin program will be funded by ADT using Small Business Innovation Research (“SBIR”) grants to ADT.We

believe we are positioned for the successful development of small molecule inhibitors.

We believe that our pan-RAS and PDE10/β-catenin

programs have substantial promise to lead to new development candidates with the potential to treat lethal tumors harboring RAS

and Wnt/APC/β-catenin pathway mutations in the United States and globally.

In January 2020, our board of directors

approved management’s recommendation to close our office and laboratories located in Israel.

Following the closure of the

Israeli facilities at the end of May 2020, our sole remaining office was located in Cambridge, Massachusetts.

Under circumstances

related our restructuring this office has not been in use for a large part of the year and our lease for this office in Cambridge,

Massachusetts terminated on February 28, 2021.

We are allowed, however, to continue using this address to receive mail.

On July 2, 2020, our Chief Executive

Frank Haluska, sent a letter to the Chairman of our board of directors outlining Dr.

Haluska’s belief

that events had occurred that were sufficient to trigger his ability to resign for “Good Reason”

under his employment

Our board of directors informed Dr.

Haluska that it disagreed with the letter’s assertions regarding “Good

Reason”

and treated the letter as a constructive resignation effective as of July 2, 2020.

On July 12, 2020, Dr.

Haluska tendered his written resignation from our board of directors, effective immediately.

Haluska referenced the matters

articulated in his letter of July 2, 2020, and the Company’s response and actions following receipt of the letter as

the basis for his resignation from the Board.

It is our position, based on advice from our legal counsel, that Dr.

resigned without Good Reason, is not entitled to severance, and we will contest any and all claims for severance.

appointment of Mr.

Neil Cohen as interim Chief Executive Officer in October 2020 (see below), our board of directors

handled all matters related to CEO duties.

On October 20, 2020, we appointed

Neil Cohen as interim Chief Executive Officer of Anchiano, effective immediately.

Cohen continues to serve as

a member of our board of directors.

The Company also appointed Andrew Fine to serve as our Chief Financial Officer, effective

Fine previously served as our Interim Chief Financial Officer pursuant to a subcontracting agreement.

In light of business circumstances, and

in order to conserve cash and preserve optionality while alternatives are being identified and assessed, we made a decision during

July 2020 to undertake reductions in headcount and other cost saving measures.

These included plans to temporarily reduce

our internal and external research and development work on the Company’s pan-RAS-inhibitor program until there is greater

clarity regarding Anchiano’s ability to fund the program.

We continue to undertake actions for the promotion of the program

and its assets and towards strengthening the protection of all related intellectual property.

On December 14, 2020 we entered into

an Agreement and Plan of Merger with Chemomab, an Israeli limited company and a clinical-stage biotech company focusing on the

discovery and development of innovative therapeutics for fibrosis-related diseases with high unmet need, which included the proposed

Merger of CMB Acquisition Ltd., a wholly owned subsidiary of ours, with Chemomab as the surviving company, subject to shareholder

A shareholder meeting has been scheduled for March 15, 2021 to approve the Merger and related proposals.

information regarding Chemomab and the proposed Merger, see the proxy statement/prospectus we filed with the SEC on February 12,

2021 and that can be found at this link:

https://www.sec.gov/Archives/edgar/data/1534248/000110465921021553/tm211883-6_424b3.htm

Our Product Pipeline

Our preclinical

programs are summarized below and consist of two preclinical programs.

We have a partnership with ADT related to two small molecule

development programs targeting oncogenic pathways, focused on RAS and PDE10/β-catenin, respectively.

Our preclinical programs are summarized

below and consist of two preclinical programs.

We have a partnership with ADT related to two small molecule development programs

targeting oncogenic pathways, focused on RAS and PDE10/β-catenin, respectively.

Our Therapeutics Pipeline

Pan-RAS Program :

Our highest priority program targets oncogenic mutations in the RAS family of genes ( i.e.

, KRAS, HRAS, and NRAS gene families),

which are present in more than 30% of cancers.

RAS plays a pivotal role in signal transduction pathways leading to tumor cell proliferation

and survival.

Our pan-RAS program has identified novel indene-based small molecules that exhibit potent and selective inhibition

of activated RAS signaling regardless of isoform or mutation, or pan-RAS inhibition.

PDE10/ß-catenin Program :

Genetic alterations in components that make up the Wnt signaling pathway, which includes APC and β-catenin, are prevalent

in a number of cancer types, occurring in more than 80% of colorectal cancers.

Our PDE10/ß-catenin program has identified

small molecules that selectively and potently inhibit PDE10 and suppress Wnt/APC/β-catenin signaling in preclinical models.

HRAS, and NRAS gene families), which are present in more than 30% of cancers.

RAS plays a pivotal role in signal transduction

pathways leading to tumor cell proliferation and survival.

Our pan-RAS program has identified novel indene-based small molecules

that exhibit potent and selective inhibition of activated RAS signaling regardless of isoform or mutation, or pan-RAS inhibition.

PDE10/ß-catenin

Genetic alterations in components that make up the Wnt signaling pathway, which includes APC and β-catenin,

are prevalent in a number of cancer types, occurring in more than 80% of colorectal cancers.

Our PDE10/ß-catenin program

has identified small molecules that selectively and potently inhibit PDE10 and suppress Wnt/APC/β-catenin signaling in preclinical

PDE10 inhibition has been shown to down regulate β-catenin expression and inhibits polyp and tumor growth.

We believe it has

potential for application in the treatment of cancer as well as spontaneous and familial polyposis syndromes.

Inodiftagene vixteplasmid :

Previously we discovered

and developed a gene therapy, inodiftagene, designed to treat non-muscle invasive bladder cancer (“NMIBC”).

developed this gene therapy in six clinical trials in pancreatic cancer, ovarian cancer, and bladder cancer.

Based on these preliminary

clinical studies, we determined to test this product candidate in a clinical trial designed as the basis for potential regulatory

This clinical trial, the Codex trial, was initiated in December 2018, enrolling patients through the following year.

In November 2019, we discontinued the pivotal Phase 2 Codex study.

After a thorough analysis of the data, we determined that there

was a low probability of surpassing the pre-defined futility threshold at the planned interim analysis, which required 10 complete

responses in 35 patients.

As of November 14, 2019, 16 patients were evaluable after the first disease assessment on treatment;

of these, three, or 19%, had experienced a complete response.

The data also indicated a low probability of achieving an efficacy

profile that in our estimation would be necessary to support regulatory approval.

The safety data on the investigational product

were consistent with those observed in prior preliminary clinical trials.

While no further clinical development is currently planned,

we maintain rights to inodiftagene, licensed from Yissum Research Development Company of the Hebrew University of Jerusalem (“Yissum”),

and may evaluate strategic options, including out-licensing or partnering opportunities, with the therapy in other NMIBC or oncology

indications, subject to the terms of the Yissum agreement.

it has potential for application in the treatment of cancer as well as spontaneous and familial polyposis syndromes.

vixteplasmid :

Previously we discovered and developed a gene therapy, inodiftagene, designed to treat non-muscle

invasive bladder cancer (“NMIBC”).

We had developed this gene therapy in six clinical trials in pancreatic cancer,

ovarian cancer, and bladder cancer.

Based on these preliminary clinical studies, we determined to test this product candidate

in a clinical trial designed as the basis for potential regulatory approval.

This clinical trial, the Codex trial, was initiated

in December 2018, enrolling patients through the following year.

In November 2019, we discontinued the pivotal Phase

2 Codex study.

After a thorough analysis of the data, we determined that there was a low probability of surpassing the pre-defined

futility threshold at the planned interim analysis, which required 10 complete responses in 35 patients.

As of November 14,

2019, 16 patients were evaluable after the first disease assessment on treatment;

of these, three, or 19%, had experienced a complete

The data also indicated a low probability of achieving an efficacy profile that in our estimation would be necessary

to support regulatory approval.

The safety data on the investigational product were consistent with those observed in prior preliminary

clinical trials.

In April 2020 we notified Yissum Technology Transfer Company of the Hebrew University Ltd.

(“Yissum”)

that as a result of our decision to discontinue clinical development of inodiftagene, we will cease payments to maintain intellectual

property (“IP”) we licensed from Yissum that supported the development and as related to a licensing and development

agreement between the parties (“License Agreement”).

In August 2020 we agreed with Yissum on termination of the

License Agreement and return of the IP.

Pan-RAS Program

to the National Cancer Institute, mutations in the RAS family of genes ( i.e.

, KRAS, HRAS, and NRAS) are the most frequent

oncogenic mutations in cancer, present in over 30% of all cancers.

These mutations are involved in more than 181,000 cancer deaths

per year (more than 30% of 606,000 deaths) in the United States alone.

The three most lethal cancers, lung cancer, colorectal cancer

and pancreatic cancer, are driven largely by mutant RAS.

Of these cancer types, non-small cell lung cancers (“NSCLC”)

have mutations in the RAS family of genes in approximately 35% of cases;

colorectal cancers carry RAS mutation in approximately

45% of cases;

and pancreatic cancers carry RAS mutations in over 95% of cases.

Taken together, in these three cancer types, RAS

mutations account for more than 100,000 lethal cases of cancer per year in the United States.

The World Health Organization estimates

that in 2018, the most common causes of cancer death are lung cancer (1.76 million deaths) and colorectal cancer (862,000 deaths).

According to the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program, five-year survival outcomes

in advanced NSCLC, colorectal cancer and pancreatic cancer are particularly dismal - 5%, 14% and 3%, respectively.

that the total addressable population of patients with RAS-mutation driven solid tumors alone totals more than 165,000 patients

per year in the United States.

These morbidity and mortality rates suggest that therapies directed at tumors carrying mutated forms

of RAS are urgently needed.

together, these statistics suggest that the patient population that could benefit from effective therapy targeting RAS mutations

annual incidence of NSCLC, colorectal cancer, and pancreatic cancer combined is approximately 395,000 patients,

of which approximately 295,00 are advanced cases.

We estimate that this translates into approximately 130,000 addressable patients

annually with RAS-mutated advanced solid tumors in the United States in these three indications.

We estimate that other solid tumors

will add approximately 35,000 additional addressable patients for a total annual addressable patient population of 165,000 in the

United States.

RAS mutations are similarly frequent globally.

Despite success in development of therapies targeting other genetic

drivers in cancer, there have been no approved RAS inhibitors to date.

The frequency of RAS mutations in cancer, the high mortality

associated with the disease, and the lack of any approved targeted therapies creates a significant clinical need.

a pivotal role in cell signal transduction pathways leading to tumor cell proliferation and survival.

RAS, a membrane bound protein,

resides in an inactive, or GDP-bound, state.

Following stimulation, RAS releases guanosine triphosphate (“GDP”) and

forms a transient nucleotide-free state, subsequently binding with guanosine triphosphate (“GTP”).

Active, or GTP-bound,

RAS engages specific RAS effector proteins ( e.g.

, RAF, PI3K), resulting in activation of pathways leading to cell proliferation

and survival.

Oncogenic activation of RAS occurs mainly via mutations in codons 12, 13 and 61—with a shift to the GTP-bound

state and constitutive activation of RAS effector pathways.

According to the National Cancer Institute,

mutations in the RAS family of genes ( i.e.

, KRAS, HRAS, and NRAS) are the most frequent oncogenic mutations in cancer,

present in over 30% of all cancers.

These mutations are involved in more than 181,000 cancer deaths per year (more than 30% of

606,000 deaths) in the United States alone.

The three most lethal cancers, lung cancer, colorectal cancer and pancreatic cancer,

are driven largely by mutant RAS.

Of these cancer types, non-small cell lung cancers (“NSCLC”) have mutations in the

RAS family of genes in approximately 35% of cases;

colorectal cancers carry RAS mutation in approximately 45% of cases;

and pancreatic

cancers carry RAS mutations in over 95% of cases.

Taken together, in these three cancer types, RAS mutations account for more

than 100,000 lethal cases of cancer per year in the United States.

The World Health Organization estimates that in 2018, the most

common causes of cancer death are lung cancer (1.76 million deaths) and colorectal cancer (862,000 deaths).

According to the National

Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program, five-year survival outcomes in advanced NSCLC, colorectal

cancer and pancreatic cancer are particularly dismal - 5%, 14% and 3%, respectively.

We estimate that the total addressable

population of patients with RAS-mutation driven solid tumors alone totals more than 165,000 patients per year in the United States.

These morbidity and mortality rates suggest that therapies directed at tumors carrying mutated forms of RAS are urgently needed.

Taken together, these statistics suggest

that the patient population that could benefit from effective therapy targeting RAS mutations is large.

annual incidence

of NSCLC, colorectal cancer, and pancreatic cancer combined is approximately 395,000 patients, of which approximately 295,00 are

advanced cases.

We estimate that this translates into approximately 130,000 addressable patients annually with RAS-mutated advanced

solid tumors in the United States in these three indications.

We estimate that other solid tumors will add approximately 35,000

additional addressable patients for a total annual addressable patient population of 165,000 in the United States.

RAS mutations

are similarly frequent globally.

Despite success in development of therapies targeting other genetic drivers in cancer, there

have been no approved RAS inhibitors to date.

The frequency of RAS mutations in cancer, the high mortality associated with the

disease, and the lack of any approved targeted therapies creates a significant clinical need.

RAS plays a pivotal role in cell signal

transduction pathways leading to tumor cell proliferation and survival.

RAS, a membrane bound protein, resides in an inactive,

or GDP-bound, state.

Following stimulation, RAS releases guanosine triphosphate (“GDP”) and forms a transient nucleotide-free

state, subsequently binding with guanosine triphosphate (“GTP”).

Active, or GTP-bound, RAS engages specific RAS effector

proteins ( e.g.

, RAF, PI3K), resulting in activation of pathways leading to cell proliferation and survival.

Oncogenic activation

of RAS occurs mainly via mutations in codons 12, 13 and 61—with a shift to the GTP-bound state and constitutive activation

of RAS effector pathways.

RAS Signaling Pathway

Abbreviations:

epidermal growth factor receptor,

extracellular signal-regulated kinase

growth factor receptor-bound protein 2

mitogen activated protein kinase

growth factor receptor,

extracellular

signal-regulated kinase

growth factor receptor-bound

mitogen activated

protein kinase

phosphorylated

phosphatidylinositol 3-kinase

phosphatidylinositol (4,5)-bisphosphate

phosphatidylinositol (3,4,5)-trisphosphate

phosphatidylinositol

(4,5)-bisphosphate

phosphatidylinositol

(3,4,5)-trisphosphate

son of sevenless

15 unchanged sentences

trials ( e.g.

, Amgen Inc.’s AMG-510 and Mirati Therapeutics, Inc.’s MRTX849), with early clinical data reporting

evidence of activity in KRAS G12C mutation-positive cancers, particularly NSCLC.

These drugs have generated enormous excitement,

with the most advanced drug, AMG-510, showing an overall response rate (“ORR”) of 48% in 23 evaluable NSCLC patients

with eight out of 11 responders remaining in response and on treatment.

Similarly, MRTX849 has shown a 50% ORR in six patients

with NSCLC in its initially presented Phase 1 data set.

, Amgen Inc.’s AMG-510 and Mirati Therapeutics, Inc.’s MRTX849), with early clinical data

reporting evidence of activity in KRAS G12C mutation-positive cancers, particularly NSCLC.

These drugs have generated enormous

excitement, with the most advanced drug, AMG-510, showing an overall response rate (“ORR”) of 48% in 23 evaluable

NSCLC patients with eight out of 11 responders remaining in response and on treatment.

Similarly, MRTX849 has shown a 50% ORR

in six patients with NSCLC in its initially presented Phase 1 data set.

We believe the significance of these successes

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Adapted from:

Nat Rev Drug Discov, 2014

Frequency of Specific KRAS

mutations in KRAS-Mutated Lung, Colorectal, Pancreatic and Biliary Tract Cancers

Cox et al., Nat Rev Drug Discov, 2014

Frequency of Specific KRAS mutations in KRAS-Mutated Lung,

Colorectal, Pancreatic and Biliary Tract Cancers

Adapted from:

Vasan et al., Clinical cancer research,

that our pan-RAS program is poised to take advantage both of the fact that RAS inhibition has been shown to be clinically valid,

and that initial successes have been confined to a fraction of tumors that carry RAS mutations.

A broadly acting RAS inhibitor

with the potential to treat RAS-driven cancers regardless of RAS isoform or mutation ( i.e ., a pan-RAS inhibitor) would be

clinically useful.

It is also not yet well understood what resistance mechanisms to KRAS G12C mutation inhibitors will develop

in the clinic.

A pan-RAS inhibitor may be clinically preferable in KRAS G12C mutation-positive patients if resistance to KRAS G12C

mutation inhibitors leads to mutations in other RAS isoforms or other KRAS mutations, and may also have utility in such patients

who have been treated previously with a KRAS G12C mutation inhibitor.

There is a clear need to continue to develop new and more

effective direct inhibitors of RAS, preferably with broad activity against the multiple RAS isoforms and various mutations.

the frequency of RAS mutations overall, a pan-RAS inhibitor would have potential to address a substantial proportion of cancer

patients—significantly more than any other genetic target for which drugs have been developed to date (and, we estimate,

approximately 11 times more patients than are addressable by the KRAS G12C mutation inhibitors).

Therefore, our pan-RAS program

is our highest priority.

We believe that our pan-RAS program is

poised to take advantage both of the fact that RAS inhibition has been shown to be clinically valid, and that initial successes

have been confined to a fraction of tumors that carry RAS mutations.

A broadly acting RAS inhibitor with the potential to treat

RAS-driven cancers regardless of RAS isoform or mutation ( i.e ., a pan-RAS inhibitor) would be clinically useful.

also not yet well understood what resistance mechanisms to KRAS G12C mutation inhibitors will develop in the clinic.

inhibitor may be clinically preferable in KRAS G12C mutation-positive patients if resistance to KRAS G12C mutation inhibitors

leads to mutations in other RAS isoforms or other KRAS mutations, and may also have utility in such patients who have been treated

previously with a KRAS G12C mutation inhibitor.

There is a clear need to continue to develop new and more effective direct inhibitors

of RAS, preferably with broad activity against the multiple RAS isoforms and various mutations.

Given the frequency of RAS mutations

overall, a pan-RAS inhibitor would have potential to address a substantial proportion of cancer patients—significantly more

than any other genetic target for which drugs have been developed to date (and, we estimate, approximately 11 times more patients

than are addressable by the KRAS G12C mutation inhibitors).

Therefore, our pan-RAS program is our highest priority.

Our lead RAS inhibitor molecules are novel

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present in sulindac, to lessen the potential cardiovascular side effects observed with sulindac and other related drugs.

We believe our RAS inhibitor molecules have

potential for RAS inhibition in a broad variety of clinical settings, because they exhibit the characteristics we believe are necessary

in a pan-RAS inhibitor.

Our RAS inhibitor molecules potently, selectively, and reversibly inhibit growth of tumor cells harboring

mutant RAS, while having greater than 100-fold selectivity over cells with normal RAS activity.

Inhibitory activity has been observed

with low nanomolar potency (<10 nM) in KRAS-, HRAS-, and NRAS-driven models with a variety of mutations (e.g.

KRAS G12C, G13D,

and NRAS Q61K) across a variety of tumor types, which suggests that these molecules could have utility across

the broad spectrum of RAS mutations and tumor types in which these mutations have been observed to drive cancer.

This potent activity

is observable in both monolayer cultures, and in 3-D spheroid cultures, which may have higher predictive value for anti-tumor activity.

These compounds inhibit downstream signaling through RAF and PI3K pathways, which is consistent with their acting directly on RAS,

as opposed to another pathway molecule.

They initiate cell-cycle arrest and induce apoptosis, consistent with cell killing.

the inhibitors demonstrate blockade of GTP loading of RAS in the nucleotide-free state in cell-free biochemical assays, suggesting

that their mechanism of action is through interference of GTP-mediated signaling.

They have exhibited in vivo activity in

RAS mutant tumor models.

Finally, an emerging characteristic of RAS inhibition is the stimulation of anti-tumor immunity.

has been shown with AMG 510, a KRAS G12C inhibitor presently in the clinic, and it suggests that effective RAS inhibition stimulates

several anti-tumor immune mechanisms.

Our inhibitors have been shown to similarly stimulate anti-tumor T-cell-mediated immune mechanisms.

These multiple lines of evidence are all consistent with the characteristics one would expect to observe with a drug that is killing

cells by direct inhibition of RAS.

We believe our RAS inhibitor molecules

have potential for RAS inhibition in a broad variety of clinical settings, because they exhibit the characteristics we believe

are necessary in a pan-RAS inhibitor.

Our RAS inhibitor molecules potently, selectively, and reversibly inhibit growth of tumor

cells harboring mutant RAS, while having greater than 100-fold selectivity over cells with normal RAS activity.

Inhibitory activity

has been observed with low nanomolar potency (<10 nM) in KRAS-, HRAS-, and NRAS-driven models with a variety of mutations (e.g.

KRAS G12C, G13D, G12V, G12S;

and NRAS Q61K) across a variety of tumor types, which suggests that these molecules could

have utility across the broad spectrum of RAS mutations and tumor types in which these mutations have been observed to drive cancer.

This potent activity is observable in both monolayer cultures, and in 3-D spheroid cultures, which may have higher predictive

value for anti-tumor activity.

These compounds inhibit downstream signaling through RAF and PI3K pathways, which is consistent

with their acting directly on RAS, as opposed to another pathway molecule.

They initiate cell-cycle arrest and induce apoptosis,

consistent with cell killing.

Importantly, the inhibitors demonstrate blockade of GTP loading of RAS in the nucleotide-free state

in cell-free biochemical assays, suggesting that their mechanism of action is through interference of GTP-mediated signaling.

They have exhibited in vivo activity in RAS mutant tumor models.

Finally, an emerging characteristic of RAS inhibition

is the stimulation of anti-tumor immunity.

This has been shown with AMG 510, a KRAS G12C inhibitor presently in the clinic, and

it suggests that effective RAS inhibition stimulates several anti-tumor immune mechanisms.

Our inhibitors have been shown to similarly

stimulate anti-tumor T-cell-mediated immune mechanisms.

These multiple lines of evidence are all consistent with the characteristics

one would expect to observe with a drug that is killing cells by direct inhibition of RAS.

We believe these molecules have potential

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Over the next 12-18 months our main goals are to understand the specific

mechanism of action and physical basis of binding of the compounds to RAS, and to optimize the initially identified series of compounds

to identify a lead development candidate.

mechanism of action and physical basis of binding of the compounds to RAS, and to optimize the initially identified series of

compounds to identify a lead development candidate.

One of our lead compounds in the pan-RAS

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Cell lines with wild-type (“WT”) RAS and concurrent upstream mutations (e.g.

EGFR) that signal through

RAS display similar inhibition to cell lines with mutated RAS.

Cell lines with WT RAS in the absence of upstream activation are

less sensitive (>100-fold selectivity), regardless of downstream activating mutations.

EGFR) that signal

through RAS display similar inhibition to cell lines with mutated RAS.

Cell lines with WT RAS in the absence of upstream activation

are less sensitive (>100-fold selectivity), regardless of downstream activating mutations.

Sensitivity to ANC 007 can be conferred

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Keeton et al., AACR 2019;

Mattox et al.

McConnell et al.

Data on File.

ANC 007 has previously been referred to as MCI-062.

ANC 007 has previously been

referred to as MCI-062.

Potent and Selective RAS Inhibition of Monolayer and

Spheroid Culture with ANC 007

inhibitory activity of ANC 007 (MCI-062) was tested using the CellTiter-Glo luminescence assay.

of colony formation was tested on a five different cell lines using ANC 007.

BcPC-3 is a pancreatic cell line with non-mutated,

or wild type, RAS.

Growth inhibitory activity of ANC 007 (MCI-062) was tested using

the CellTiter-Glo luminescence assay.

Inhibition of colony formation was tested on a five different cell lines

using ANC 007.

BcPC-3 is a pancreatic cell line with non-mutated, or wild type, RAS.

Other four cell lines carry RAS mutations.

incompetent retrovirus encoding HRAS-G12V mutant or empty vector was prepared by transfection of A293T cells with packaging and

envelope plasmids.

Replication incompetent retrovirus encoding HRAS-G12V mutant or empty

vector was prepared by transfection of A293T cells with packaging and envelope plasmids.

Crude supernatant collected and used to tranduce HT29 colon cancer cells.

Stable pools of each were expanded

and expression of HRAS was characterized by western blot.

of each were expanded and expression of HRAS was characterized by western blot.

Keeton et al., AACR 2019;

1 unchanged sentence

Data on File.

has been shown to inhibit signaling through RAF and PI3K pathways ( i.e.

, nodes in the signal transduction cascade that are

downstream (distal) to RAS), which suggests that the node of inhibition is RAS itself, rather than one of the effectors further

As shown below, treatment of MIA-PaCa-2 pancreatic cancer cells with KRAS G12C results in inhibition of signaling of

the MAPK pathway as evidenced by inhibition of phosphorylation of CRAF, MEK, and ERK.

ANC 007 has been shown to inhibit signaling

through RAF and PI3K pathways ( i.e.

, nodes in the signal transduction cascade that are downstream (distal) to RAS), which

suggests that the node of inhibition is RAS itself, rather than one of the effectors further downstream.

As shown below, treatment

of MIA-PaCa-2 pancreatic cancer cells with KRAS G12C results in inhibition of signaling of the MAPK pathway as evidenced by inhibition

of phosphorylation of CRAF, MEK, and ERK.

AKT phosphorylation is also inhibited.

observation that both sides of the signaling pathways downstream from RAS (RAF/MEK/ERK and AKT) are inhibited suggests that the

node of inhibition is RAS itself, rather than one of the effectors further downstream.

MAPK signaling in KRAS G13D mutant HCT-116

colon cancer cells is inhibited in vivo as well.

The observation that both sides of the signaling

pathways downstream from RAS (RAF/MEK/ERK and AKT) are inhibited suggests that the node of inhibition is RAS itself, rather than

one of the effectors further downstream.

MAPK signaling in KRAS G13D mutant HCT-116 colon cancer cells is inhibited in vivo

Inhibition of Downstream Signaling Through RAF and PI3K

Pathways with ANC 007

A, ANC 007 (MCI-062) reduced RAS-GTP levels and inhibits activation of downstream

RAS signaling in MIA-PaCa-2 pancreatic cancer cells Cells were treated with vehicle or ANC 007 for 24 hours in serum-free media

and subsequently stimulated with 30 ng/mL EGF for 10 minutes.

RAS- GTP levels after treatment were determined by the active RAS

pull-down using GST-RAF1- RBD/glutathione agarose and detection by Western blotting.

Detection of phospho-protein levels was performed

by Western blot.

B, ANC 007 inhibits activation of downstream RAS signaling and activates anti-tumor

immunity in murine RAS mutant colon cancer model.

Mice were implanted in the right flank with 10 million HCT- 116 tumor cells per

ANC 007-treated mice received 5 mg/kg MCI-062 twice daily by peritumoral administration.

ANC 007 (MCI-062) reduced RAS-GTP levels and inhibits activation of downstream

RAS signaling in MIA-PaCa-2 pancreatic cancer cells Cells were treated with vehicle or

ANC 007 for 24 hours in serum-free media and subsequently stimulated with 30 ng/mL EGF

for 10 minutes.

RAS- GTP levels after treatment were determined by the active RAS pull-down

using GST-RAF1- RBD/glutathione agarose and detection by Western blotting.

of phospho-protein levels was performed by Western blot.

ANC 007 inhibits activation of downstream RAS signaling and activates

anti-tumor immunity in murine RAS mutant colon cancer model.

Mice were implanted in the

right flank with 10 million HCT- 116 tumor cells per mouse.

ANC 007-treated mice received

5 mg/kg MCI-062 twice daily by peritumoral administration.

Vehicle-treated mice received

5% DMSO/5% cremophor EL/90% water once daily by peritumoral administration.

RAS-GTP levels in tumor lysates were determined by the

active RAS pull-down and detection by Western blotting.

RAS-GTP levels

in tumor lysates were determined by the active RAS pull-down and detection by Western

Levels of MAPK proteins and immune markers were determined by Western blotting

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Each lane corresponds to an individual animal.

et al., AACR 2019;

Keeton et al., AACR 2019;

Mattox et al.

characterize the molecular mechanism of action of ANC 007, it has been tested in cell-free biochemical assays utilizing recombinant

KRAS in order to evaluate the potential for direct binding of the drug to the RAS protein.

To initially characterize

the molecular mechanism of action of ANC 007, it has been tested in cell-free biochemical assays utilizing recombinant KRAS in

order to evaluate the potential for direct binding of the drug to the RAS protein.

Incubation of ANC 007 with nucleotide-free

KRAS followed by addition of GTP led to a concentration dependent reduction of RAS-GTP levels in an RBD pull-down experiment.

effect was not observed when ANC 007 was incubated with GTP-loaded RAS.

The RBD assay utilizes the Ras-binding domain (RBD) of

the RAS effector kinase Raf1 which been shown to bind specifically to the GTP-bound form of RAS proteins, making it an ideal tool

for affinity purification of GTP-Ras.

This experiment suggests ANC 007 directly inhibits GTP binding to RAS when RAS is in the

nucleotide-free state but not in the GTP-bound state.

This effect was not observed when ANC 007 was incubated with GTP-loaded RAS.

The RBD assay utilizes the Ras-binding domain (RBD)

of the RAS effector kinase Raf1 which been shown to bind specifically to the GTP-bound form of RAS proteins, making it an ideal

tool for affinity purification of GTP-Ras.

This experiment suggests ANC 007 directly inhibits GTP binding to RAS when RAS is in

the nucleotide-free state but not in the GTP-bound state.

Similarly, in a guanine nucleotide exchange assay, which uses a fluorescently-labeled

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Biochemical Assays Under Nucleotide-Free (nf) Conditions with ANC 007

A, ANC 007 (MCI-062) inhibits GTP binding to recombinant nucleotide-free RAS in RBD

pull-down experiment.

Nucleotide-free recombinant WT-KRAS was prepared by incubation with 20 mM EDTA on ice.

ANC 007 or vehicle

was incubated 1 h with nucleotide-free WT-KRAS, followed by addition of GTP and an additional 30 min incubation (left) or, ANC

ANC 007 (MCI-062) inhibits GTP binding to recombinant nucleotide-free

RAS in RBD pull-down experiment.

Nucleotide-free recombinant WT-KRAS was prepared by

incubation with 20 mM EDTA on ice.

ANC 007 or vehicle was incubated 1 h with nucleotide-free

WT-KRAS, followed by addition of GTP and an additional 30 min incubation (left) or, ANC

007 was incubated with WT-KRAS after addition of GTP (GTP-bound, right).

RAS-GTP levels after treatment were determined by the

active RAS pull-down assay using GST-RAF1-RBD/glutathione agarose and detection by Western blotting.

B, ANC 007 inhibits GTP binding to recombinant nucleotide-free RAS in guanine nucleotide

exchange assay.

Nucleotide-free recombinant WT-KRAS was prepared by incubation with 20 mM EDTA on ice.

Nucleotide free KRAS

was incubated with ANC 007 or vehicle for 1 h on ice, followed by addition of an excess of MgCl 2 with fluorogenic MANT-GTP.

Recombinant KRAS not treated with EDTA (GTP-KRAS) was included as a control indicator of intrinsic turnover rate.

The development

of fluorescence reflecting MANT-GTP binding to KRAS was monitored over the course of a 45 min incubation.

RAS-GTP levels

after treatment were determined by the active RAS pull-down assay using GST-RAF1-RBD/glutathione

agarose and detection by Western blotting.

ANC 007 inhibits GTP binding to recombinant nucleotide-free RAS in guanine

nucleotide exchange assay.

Nucleotide-free recombinant WT-KRAS was prepared by incubation

with 20 mM EDTA on ice.

Nucleotide free KRAS was incubated with ANC 007 or vehicle for

1 h on ice, followed by addition of an excess of MgCl 2 with fluorogenic MANT-GTP.

Recombinant KRAS not treated with EDTA (GTP-KRAS) was included as a control indicator

of intrinsic turnover rate.

The development of fluorescence reflecting MANT-GTP

binding to KRAS was monitored over the course of a 45 min incubation.

Mattox et al.

Data on File.

has exhibited potent anti-tumor activity in RAS-driven tumor models in mice, consistent with the cell based in vitro data.

As shown below, ANC 007 inhibited tumor growth by intratumoral administration in KRAS mutant colon tumor xenograft models (HCT116

and CT26 cell lines).

ANC 007 has exhibited potent anti-tumor

activity in RAS-driven tumor models in mice, consistent with the cell based in vitro data.

As shown below, ANC 007 inhibited

tumor growth by intratumoral administration in KRAS mutant colon tumor xenograft models (HCT116 and CT26 cell lines).

In Vivo Antitumor Activity in RAS-driven Tumor Models

ANC 007 (MCI-062) inhibits growth of KRAS mutant HCT-116 tumor cells in a subcutaneous

mouse xenograft model.

Athymic nude mice were implanted in the right flank with 10 million tumor cells per mouse.

Mice were treated

once daily by intratumoral administration.

ANC 007 (MCI-062) inhibits growth of KRAS mutant HCT-116 tumor cells in

a subcutaneous mouse xenograft model.

Athymic nude mice were implanted in the right flank

with 10 million tumor cells per mouse.

Mice were treated once daily by intratumoral administration.

Control mice received vehicle only (5% DMSO/5% cremophor EL/90% water) once daily by

intratumoral administration.

N=8 mice for vehicle group, n=7 mice for 5 mg/kg ANC 007 group, n=4 mice for 10 mg/kg ANC 007 group.

Mice were implanted in the right flank with one million CT-26 tumor cells per mouse.

N=8 mice for vehicle group, n=7 mice for 5 mg/kg ANC 007

group, n=4 mice for 10 mg/kg ANC 007 group.

Mice were implanted in the right flank with one million CT-26 tumor cells

ANC 007 treated mice received 5 mg/kg ANC 007 twice daily by peritumoral administration.

Vehicle-treated mice received 5% DMSO/5%

cremophor EL/90% water once daily by peritumoral administration.

Shown on left is control (vehicle-treated) mice and on the right

are mice treated with ANC 007.

below, in an immune competent mouse RAS-mutant tumor model, ANC 007 suppressed tumor growth in association with decreased PD-L1

levels in tumors;

decreased PD-1 in T-cells;

Vehicle-treated mice received 5% DMSO/5% cremophor EL/90% water once daily by peritumoral

administration.

Shown on left is control (vehicle-treated) mice and on the right are

mice treated with ANC 007.

As shown below, in an immune competent

mouse RAS-mutant tumor model, ANC 007 suppressed tumor growth in association with decreased PD-L1 levels in tumors;

PD-1 in T-cells;

increased proportion of CD4+ and CD8+ T-cells in tumors;

and reduced Treg cells in

tumors (as evidenced by Foxp3 expression).

Similar effects on the tumor immune microenvironment have been observed with KRAS G12C

inhibitors, including AMG-510, and this stimulation of anti-tumor immunity appears to be an emerging characteristic of RAS inhibition

These lines of evidence suggest that effective RAS inhibition stimulates several anti-tumor immune mechanisms., and ANC

007 has been shown to similarly stimulate these anti-tumor T-cell-mediated immune mechanisms.

and reduced Treg cells in tumors (as evidenced by Foxp3

Similar effects on the tumor immune microenvironment have been observed with KRAS G12C inhibitors, including AMG-510,

and this stimulation of anti-tumor immunity appears to be an emerging characteristic of RAS inhibition itself.

These lines of

evidence suggest that effective RAS inhibition stimulates several anti-tumor immune mechanisms., and ANC 007 has been shown to

similarly stimulate these anti-tumor T-cell-mediated immune mechanisms.

Inhibition of Tumor Growth with ANC 007 Associated with

Activation of Antitumor Immunity

ANC 007 (MCI-062) reduces PD-L1 expression in RAS driven tumor model.

implanted in the right flank with one million CT26 tumor cells per mouse.

ANC 007-treated mice received 5 or 10 mg/kg ANC 007 once

daily by intratumoral administration.

Vehicle-treated mice received 5% DMSO/5% cremophor EL/90% water once daily by intratumoral

administration.

RAS-GTP levels in tumor lysates were determined by the active RAS pull-down and detection by Western blotting.

ANC 007 (MCI-062) reduces

PD-L1 expression in RAS driven tumor model.

Mice were implanted in the right flank with one million CT26 tumor cells per mouse.

ANC 007-treated mice received 5 or 10 mg/kg ANC 007 once daily by intratumoral administration.

Vehicle-treated mice received

5% DMSO/5% cremophor EL/90% water once daily by intratumoral administration.

RAS-GTP levels in tumor lysates were determined

by the active RAS pull-down and detection by Western blotting.

of immune markers was performed on whole tumor lysate.

007 reduces PD-1, increases proportion of CD4+ and CD8+ T-cells, and reduces Tregs.

Subcutaneous CT-26 murine tumors were excised

from vehicle or ANC 007 treated mice, and digested for 1 h using the gentle-MACS dissociator and murine tumor digestion protease

Following digestion, single cell suspensions were recovered by passage through a cell strainer, and cell counts

were normalized by quantitation using a hemacytometer.

Fluorescently labelled antibodies used to quantitate the indicated

cell populations by flow cytometry.

ANC 007 reduces PD-1, increases proportion of CD4+ and CD8+ T-cells, and reduces Tregs.

Subcutaneous CT-26

murine tumors were excised from vehicle or ANC 007 treated mice, and digested for 1 h using the gentle-MACS dissociator and

murine tumor digestion protease cocktail.

Following digestion, single cell suspensions were recovered by passage through

a cell strainer, and cell counts were normalized by quantitation using a hemacytometer.

Fluorescently labelled antibodies

used to quantitate the indicated cell populations by flow cytometry.

Preclinical Development

We are developing a series of compounds

that exhibit pan-RAS inhibition as detailed in the experiments above.

The lead compounds demonstrate low nM IC50 potency against

all RAS isoforms and all mutants tested, in cell lines of several histologies, and in monolayers and spheroids;

inhibit RAS signaling;

We initiated development of a series of

compounds that exhibit pan-RAS inhibition as detailed in the experiments above.

The lead compounds demonstrate low nM IC50 potency

against all RAS isoforms and all mutants tested, in cell lines of several histologies, and in monolayers and spheroids;

RAS signaling;

induce cell cycle arrest and apoptosis;

inhibit binding of GTP to nucleotide-free RAS;

bind to the GTP catalytic domain, in computational

structural studies;

bind to the GTP catalytic

domain, in computational structural studies;

inhibit mutant RAS-driven tumor growth in vivo ;

and demonstrate in vivo activation of anti-tumor

immunity that includes the down-regulation of PD-L1.

Over the next 12-18 months we plan to (1) replicate and expand on the data

generated previously by ADT, including further characterization of the biological activity of the compounds;

(2) undertake structural

biology investigations to understand the specific mechanism of action and physical basis of the compounds binding to RAS;

optimize the initially identified series of compounds, including ANC 007, to identify a lead development candidate for further

preclinical and then clinical development.

The preclinical work will be primary performed by a contract research organization(s)

(“CRO”), with oversight and strategic guidance by us.

and demonstrate in vivo

activation of anti-tumor immunity that includes the down-regulation of PD-L1.

Over the next 12-18 months we plan to (1) replicate

and expand on the data generated previously by ADT, including further characterization of the biological activity of the compounds;

(2) undertake structural biology investigations to understand the specific mechanism of action and physical basis of the

compounds binding to RAS;

and (3) optimize the initially identified series of compounds, including ANC 007, to identify a

lead development candidate for further preclinical and then clinical development.

The preclinical work will be primary performed

by a contract research organization(s) (“CRO”), with oversight and strategic guidance by us.

We have internally initiated experiments

5 unchanged sentences

is to gain a detailed understanding of their mechanism of action and binding to RAS.

To that end, we have embarked on a suite of

biophysical and structural biology studies, including techniques such as nano differential scanning fluorimetry (nanoDSF), microscale

thermophoresis (MST), protein nuclear magnetic resonance (NMR) and x-ray crystallography to understand specifically how these compounds

bind to the RAS protein.

This data will be crucial to understanding how this family of compounds exert their effect and learnings

will be integrated into the medicinal chemistry strategy in order to develop an optimized product candidate.

ANC 007 and related

compounds require further optimization in order to identify a suitable clinical candidate.

Evaluation of orally bioavailable candidates

will include work up of ADME (absorption, distribution, metabolism, and excretion) profile, in vivo pharmacokinetic profile

and efficacy, as well as initial assessment of in vivo toxicity.

From the time of lead candidate nomination, we anticipate

that it will take approximately 12 months to perform IND-enabling studies and submit an IND for First in Human studies, which we

would anticipate to commence in 2022.

To that end, we have embarked on a suite

of biophysical and structural biology studies, including techniques such as nano differential scanning fluorimetry (nanoDSF),

microscale thermophoresis (MST), protein nuclear magnetic resonance (NMR) and x-ray crystallography to understand specifically

how these compounds bind to the RAS protein.

This data will be crucial to understanding how this family of compounds exert their

effect and learnings will be integrated into the medicinal chemistry strategy in order to develop an optimized product candidate.

ANC 007 and related compounds require further optimization in order to identify a suitable clinical candidate.

Evaluation of orally

bioavailable candidates will include work up of ADME (absorption, distribution, metabolism, and excretion) profile, in vivo

pharmacokinetic profile and efficacy, as well as initial assessment of in vivo toxicity.

From the time of lead candidate

nomination, we anticipate that it will take approximately 12 months to perform IND-enabling studies and submit an IND for First

in Human studies, which we would anticipate to commence in 2022.

Clinical Development Plan and Regulatory Pathway

Clinical development will be initiated once

a lead product candidate has been nominated, all necessary IND-enabling studies have been performed and an IND application has

been successfully submitted to and accepted by the U.S.

Clinical development will be initiated

once a lead product candidate has been nominated, all necessary IND-enabling studies have been performed and an IND application

has been successfully submitted to and accepted by the U.S.

Food and Drug Administration (“FDA”) and adequate financing

has been secured.

Initial Phase 1 clinical investigation will be performed in patients with advanced solid tumors harboring a RAS

mutation, with the objective of identifying a recommended Phase 2 dose and to evaluate the safety and tolerability of the product

candidate, as well as to evaluate preliminary anti-tumor activity.

Given the initial clinical activity observed in lung cancer

with the KRAS G12C inhibitors in the clinic, we anticipate that NSCLC may be an area of initial focus, as well as colorectal and

pancreatic cancer (given the prevalence of RAS mutations in these cancers).

Initial Phase 1 clinical investigation will be performed in patients with advanced solid tumors harboring a

RAS mutation, with the objective of identifying a recommended Phase 2 dose and to evaluate the safety and tolerability of the

product candidate, as well as to evaluate preliminary anti-tumor activity.

Given the initial clinical activity observed in lung

cancer with the KRAS G12C inhibitors in the clinic, we anticipate that NSCLC may be an area of initial focus, as well as colorectal

and pancreatic cancer (given the prevalence of RAS mutations in these cancers).

However, we anticipate that this study would enroll

patients with multiple tumor types as long as a RAS mutation is present.

The clinical development path of other targeted

therapies in genetically defined tumors, such as those with EGFR, ALK, ROS1 and TRK aberrations, suggest that there exists the

opportunity for accelerated clinical development of a RAS inhibitor as well, provided the investigational drug exhibits high response

rate with clinically meaningful duration in a well-defined population with a significant unmet medical need.

As in these prior

examples, accelerated approval may be initially granted on the basis of a single well-executed, multi-center single arm, Phase

2 study (with the potential for different cohorts based on tumor type to support multiple indications in a single study).

the clinical proof of concept observed in NSCLC with the G12C inhibitors, we anticipate prioritizing RAS mutant NSCLC patients

The clinical development path of other

targeted therapies in genetically defined tumors, such as those with EGFR, ALK, ROS1 and TRK aberrations, suggest that there exists

the opportunity for accelerated clinical development of a RAS inhibitor as well, provided the investigational drug exhibits high

response rate with clinically meaningful duration in a well-defined population with a significant unmet medical need.

prior examples, accelerated approval may be initially granted on the basis of a single well-executed, multi-center single arm,

Phase 2 study (with the potential for different cohorts based on tumor type to support multiple indications in a single study).

Given the clinical proof of concept observed in NSCLC with the G12C inhibitors, we anticipate prioritizing RAS mutant NSCLC patients

previously treated with standard of care ( i.e ., platinum-based chemotherapy/checkpoint inhibitors) as an initial pivotal

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here may be mediated by other RAS isoforms or mutations.

A robust translational medicine effort is

needed as clinical and biomarker data may point to differential activity based on activating mutation or specific RAS gene, if

so development will need to take these considerations into account (patient selection).

A robust translational medicine effort

is needed as clinical and biomarker data may point to differential activity based on activating mutation or specific RAS gene,

if so development will need to take these considerations into account (patient selection).

An appropriately expansive clinical development

plan will contemplate how to move into investigation of first line treatment once activity is observed in the refractory setting.

Confirmatory studies for initial indication(s) can be randomized Phase 3 studies in earlier lines of therapy with standard of care

This may likely involve investigation of combination therapy, and therefore we plan for early evaluation of combination

safety and preliminary efficacy, based on tumor types showing activity in monotherapy evaluation to potentially inform confirmatory

studies and other indication expansion, depending on tumor type/setting.

Combinations may be with chemotherapy, checkpoint inhibitors

and other rational combination partners based on emerging molecular mechanisms of resistance to RAS inhibition.

Confirmatory studies for initial indication(s) can be randomized Phase 3 studies in earlier lines of therapy with standard

of care comparators.

This may likely involve investigation of combination therapy, and therefore we plan for early evaluation

of combination safety and preliminary efficacy, based on tumor types showing activity in monotherapy evaluation to potentially

inform confirmatory studies and other indication expansion, depending on tumor type/setting.

Combinations may be with chemotherapy,

checkpoint inhibitors and other rational combination partners based on emerging molecular mechanisms of resistance to RAS inhibition.

Beyond first line treatment in the advanced/metastatic

10 unchanged sentences

T790M/C797S ‘triple mutant’).

As mentioned above,

in light of business circumstances and in order to conserve cash and preserve optionality while alternatives are being identified

and assessed, we made a decision during July 2020 to undertake reductions in headcount and other cost saving measures.

included plans to temporarily reduce our internal and external research and development work on the Company’s RAS Program

until there is greater clarity regarding Anchiano’s ability to fund the program.

We continue to undertake actions for the

promotion of the program and its assets and towards strengthening the protection of all related intellectual property.

PDE10/β-catenin Program

alterations in components that make up the Wnt signaling pathway, which includes APC and β-catenin, are prevalent in a number

of cancer types, occurring in approximately 90% of colorectal cancers.

This translates into approximately 48,000 deaths annually

due to colorectal cancer carrying Wnt/APC/β-catenin pathway mutations in the Unites States alone.

Additionally, germline mutations

of APC lead to the hereditary cancer syndrome, FAP, which affects approximately 16,000 additional patients in the United States

Wnt signaling

controls the level of intracellular activated β-catenin, a key effector of oncogenic signal transduction, and oncogenic alterations

in Wnt, APC, or β-catenin all result in elevated and uncontrolled levels of β-catenin.

Wnt signaling is initiated upon

binding of secreted Wnt ligands to Frizzled receptors and low-density lipoprotein receptor-related protein (“LRP”)

co-receptors, which induces phosphorylation of Dishevelled (“Dvl”).

Phosphorylated Dvl then associates with Axin, leading

to dissociation of the β-catenin destruction complex (which includes APC and GSK3β).

Free β-catenin then accumulates

in the cytoplasm and translocates to the nucleus.

Mutations which activate the Wnt pathway all culminate in the accumulation of

high levels of oncogenic β-catenin in the cell nucleus.

Therefore, we believe a successful intervention in this pathway requires

lowering β-catenin levels or otherwise inhibiting it.

β-catenin, a transcription factor, has been considered historically

to be an “undruggable”

Genetic alterations in components that

make up the Wnt signaling pathway, which includes APC and β-catenin, are prevalent in a number of cancer types, occurring

in approximately 90% of colorectal cancers.

This translates into approximately 48,000 deaths annually due to colorectal cancer

carrying Wnt/APC/β-catenin pathway mutations in the Unites States alone.

Additionally, germline mutations of APC lead to

the hereditary cancer syndrome, FAP, which affects approximately 16,000 additional patients in the United States annually.

Wnt signaling controls the level of intracellular

activated β-catenin, a key effector of oncogenic signal transduction, and oncogenic alterations in Wnt, APC, or β-catenin

all result in elevated and uncontrolled levels of β-catenin.

Wnt signaling is initiated upon binding of secreted Wnt ligands

to Frizzled receptors and low-density lipoprotein receptor-related protein (“LRP”) co-receptors, which induces phosphorylation

of Dishevelled (“Dvl”).

Phosphorylated Dvl then associates with Axin, leading to dissociation of the β-catenin

destruction complex (which includes APC and GSK3β).

Free β-catenin then accumulates in the cytoplasm and translocates

to the nucleus.

Mutations which activate the Wnt pathway all culminate in the accumulation of high levels of oncogenic β-catenin

in the cell nucleus.

Therefore, we believe a successful intervention in this pathway requires lowering β-catenin levels or

otherwise inhibiting it.

β-catenin, a transcription factor, has been considered historically to be an “undruggable”

target, lacking the deep binding pockets present in enzymes and receptors.

As a result, drug

screening efforts have primarily focused on other pathway components.

studies have shown that PDE10 is overexpressed during early stages of tumorigenesis and is essential for tumor cell growth.

inhibition increases cyclic GMP levels in tumor cells to activate protein kinase G (PKG) signaling leading to the degradation of

the oncogenic pool of β-catenin to suppress critical proteins essential for tumor cell proliferation and survival.

foregoing reasons, we believe that targeting PDE10 provides a novel approach to selectively suppress β-catenin mediated transcriptional

As a result, drug screening efforts have primarily

focused on other pathway components.

Recent studies have shown that PDE10 is

overexpressed during early stages of tumorigenesis and is essential for tumor cell growth.

PDE10 inhibition increases cyclic GMP

levels in tumor cells to activate protein kinase G (PKG) signaling leading to the degradation of the oncogenic pool of β-catenin

to suppress critical proteins essential for tumor cell proliferation and survival.

For the foregoing reasons, we believe that

targeting PDE10 provides a novel approach to selectively suppress β-catenin mediated transcriptional activity.

Wnt/APC/β-catenin and PDE10 pathways

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Abbreviations:

5’GMP =

monophosphate

guanosine monophosphate

cyclic guanosine monophosphate

guanosine triphosphate

phosphodiesterase type 10

particulate guanylyl cyclase

protein kinase G

soluble guanylyl cyclase

T-cell factor

β-catenin program has identified small molecule indene derivatives that selectively and potently inhibit PDE10 and suppress

Wnt/APC/β-catenin signaling in preclinical models.

PDE10 inhibition has been shown to down regulate β-catenin expression

and inhibits polyp and tumor growth.

It has potential for application in the treatment of cancer as well as spontaneous and familial

polyposis syndromes.

Our orally available small molecule PDE10 inhibitors have unique advantages over known PDE10 inhibitors with

potential for development in FAP, colon, lung, liver, breast and other cancers.

of PDE10 induces cGMP/PKG signaling to phosphorylate and induce degradation of β-catenin to suppress key proteins essential

for tumor cell proliferation and survival.

PDE10 knockdown (“KD”) or inhibition with small molecules inhibits growth

and colony formation of colon, lung, and breast tumor cells.

phosphodiesterase

guanylyl cyclase

Our PDE10/ β-catenin program has identified

small molecule indene derivatives that selectively and potently inhibit PDE10 and suppress Wnt/APC/β-catenin signaling in

preclinical models.

PDE10 inhibition has been shown to down regulate β-catenin expression and inhibits polyp and tumor growth.

It has potential for application in the treatment of cancer as well as spontaneous and familial polyposis syndromes.

available small molecule PDE10 inhibitors have unique advantages over known PDE10 inhibitors with potential for development in

FAP, colon, lung, liver, breast and other cancers.

Inhibition of PDE10 induces cGMP/PKG signaling

to phosphorylate and induce degradation of β-catenin to suppress key proteins essential for tumor cell proliferation and

PDE10 knockdown (“KD”) or inhibition with small molecules inhibits growth and colony formation of colon,

lung, and breast tumor cells.

PDE10 overexpression in colon tumor cells;

blocks colony formation and ß-catenin/Tcf transcription.

Differential PDE10 levels in normal colonocytes (NCM460) and colon tumor cells

Differential PDE10 levels

in normal colonocytes (NCM460) and colon tumor cells as measured by Western blot.

PDE10 siRNA knockdown

inhibits colony formation of HT29 colon tumor cells.

PDE10 siRNA suppresses

Tcf transcription of key regulatory genes (e.g., survivin, cyclin D, myc, etc.).

Treatment of HT29 cells

with PDE10 inhibitor ANC 094 (also referred to as ADT-094) leads to reduction of ß-catenin and products of Tcf transcription

as measured by Western blot.

PDE10 siRNA knockdown inhibits colony formation of HT29 colon tumor cells.

PDE10 siRNA suppresses Tcf transcription of key regulatory genes (e.g., survivin,

cyclin D, myc, etc.).

Treatment of HT29 cells with PDE10 inhibitor ANC 094 (also referred to as ADT-094)

leads to reduction of ß-catenin and products of Tcf transcription as measured by Western blot.

Li et al., Oncogene, 2015;

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Oral administration to

mice with the Apc+/min-FCCC genotype (a mouse strain with the APC mutation that produces an augmented incidence of colorectal adenomas

and small intestinal cancers, used as a model to study polyposis syndromes and colon cancer) significantly inhibited incidence

and multiplicity of colon adenomas and carcinomas in a dose-dependent fashion.

Further in vivo studies with ANC 061 are

in progress at Fox Chase Cancer Center to confirm these findings.

These studies are funded by NCI, and if proof of concept is established

there is the potential to further develop this compound in FAP in collaboration with NCI through its PREVENT Cancer Preclinical

Drug Development Program.

mice with the Apc+/min-FCCC genotype (a mouse strain with the APC mutation that produces an augmented incidence of colorectal

adenomas and small intestinal cancers, used as a model to study polyposis syndromes and colon cancer) significantly inhibited

incidence and multiplicity of colon adenomas and carcinomas in a dose-dependent fashion.

Further in vivo studies with ANC

061 are in progress at Fox Chase Cancer Center to confirm these findings.

These studies are funded by NCI, and if proof of concept

is established there is the potential to further develop this compound in FAP in collaboration with NCI through its PREVENT Cancer

Preclinical Drug Development Program.

Inhibition of Colon Tumorigenesis in the Apc Min

A, ANC 061 (MCI-030) induced a dose dependent

decrease in adenoma incidence from 94.74% in control mice to 76.19% in mice treated with 1000 parts per million (ppm) ANC 061

and 57.80% of mice treated with 1500 ppm ANC 061.

B, Adenoma multiplicity was also significantly

reduced from 4.0 in the control group to 2.9 in mice treated with 1000 ppm ANC 061, and to 1.95 in mice treated with 1500 ppm

C, A reduction in micro adenomas was also

D, Multiplicity of flat adenomas was abolished

in mice receiving 1500 ppm and reduced in mice treated with 1000 ppm ANC 061 from 0.32 per mouse in the control group to 0.24,

respectively.

E, Incidence of mice with cancer was reduced

from 10.53% in the vehicle group to 4.76% in mice treated with 1000 ppm ANC 061 and to 0% in mice treated with 1500 ppm ANC 061,

ANC 061 (MCI-030) induced a dose dependent decrease in adenoma incidence from 94.74% in control mice to 76.19% in mice treated

with 1000 parts per million (ppm) ANC 061 and 57.80% of mice treated with 1500 ppm ANC 061.

Adenoma multiplicity was also significantly reduced from 4.0 in the control group to 2.9 in mice treated with 1000 ppm ANC

061, and to 1.95 in mice treated with 1500 ppm ANC 061.

A reduction in micro adenomas was also observed.

Multiplicity of flat adenomas was abolished in mice receiving 1500 ppm and reduced in mice treated with 1000 ppm ANC 061 from

0.32 per mouse in the control group to 0.24, respectively.

of mice with cancer was reduced from 10.53% in the vehicle group to 4.76% in mice treated with 1000 ppm ANC 061 and to 0%

in mice treated with 1500 ppm ANC 061, n=19-21.

Ward et al., AACR 2019.

compound in this program, ANC 030 (also referred to as MCI-048) administered orally inhibits tumor growth in an orthotopic lung

cancer mouse model without apparent toxicity.

ANC 030 significantly extends survival in the A549 mouse model from a median 44 to

77 days with 25% of mice surviving until the end of the experiment.

It was also effective in multiple other mouse models of lung

and breast cancer, including models of metastasis.

Another compound in this program, ANC 030

(also referred to as MCI-048) administered orally inhibits tumor growth in an orthotopic lung cancer mouse model without apparent

ANC 030 significantly extends survival in the A549 mouse model from a median 44 to 77 days with 25% of mice surviving

until the end of the experiment.

It was also effective in multiple other mouse models of lung and breast cancer, including models

of metastasis.

Inhibits Lung Tumorigenesis in A549 Lung Cancer Model

A, The A549 human lung adenocarcinoma cells with luciferase (Luc) tag were generated

using lentiviral particles expressing luciferase gene driven by a CMV promoter and a stable A549Luc clone was selected.

athymic nude mice were implanted with 1x10 6 A549Luc cells intrathoracically.

Mice were treated by oral gavage

once a day with the vehicle (Maalox) or MCI-048 at doses of 25, 50, or 100 mg/kg (n = 7/group) starting five days before tumor

cell implantation.

After implantation, treatment continued for 4 additional weeks.

Tumor growth was monitored weekly

through the detection of the bioluminescence of the A549Luc cells using In Vivo Imaging System (IVIS, IVIS Spectrum, Caliper Life

Signal intensity was quantified as the average number of photons emitted from a mouse within the chest cavity (Living

Image software, version 4.3.1.)

B, Female athymic nude mice were implanted with 1x10 6 cells per mouse of

cultured A549 human lung adenocarcinoma cells into the intrathoracic space of the left lung on Day 0.

Animals were randomly

assigned to two treatment groups (n=15) on Day 1 and treated with either MCI-048 formulated in Maalox by oral gavage at a dose

of 100 mg/kg once daily for 8 weeks or with Maalox using the same schedule starting on Day 1.

All surviving mice were euthanized

A, The A549 human lung

adenocarcinoma cells with luciferase (Luc) tag were generated using lentiviral particles expressing luciferase gene driven

by a CMV promoter and a stable A549Luc clone was selected.

Female athymic nude mice were implanted with 1x10 6 A549Luc

cells intrathoracically.

Mice were treated by oral gavage once a day with the vehicle (Maalox) or MCI-048 at doses of

25, 50, or 100 mg/kg (n = 7/group) starting five days before tumor cell implantation.

After implantation, treatment

continued for 4 additional weeks.

Tumor growth was monitored weekly through the detection of the bioluminescence of

the A549Luc cells using In Vivo Imaging System (IVIS, IVIS Spectrum, Caliper Life Sciences).

Signal intensity was quantified

as the average number of photons emitted from a mouse within the chest cavity (Living Image software, version 4.3.1.)

B, Female athymic nude

mice were implanted with 1x10 6 cells per mouse of cultured A549 human lung adenocarcinoma cells into the intrathoracic

space of the left lung on Day 0.

Animals were randomly assigned to two treatment groups (n=15) on Day 1 and treated

with either MCI-048 formulated in Maalox by oral gavage at a dose of 100 mg/kg once daily for 8 weeks or with Maalox using

the same schedule starting on Day 1.

All surviving mice were euthanized on Day 151.

Preclinical Development

We are developing a series of compounds

that exhibit potent PDE10 inhibition and induce degradation of β-catenin to suppress key proteins essential for tumor cell

proliferation and survival.

Initial plans for continued preclinical development will be funded with ADT using SBIR grants to ADT.

While we are excited by the potential for this program, we have made the decision to initially prioritize advancement of our pan-RAS

Once a product candidate has been nominated for IND-enabling studies in the pan-RAS program, we plan to allocate resources

for development of the PDE10/ β-catenin program.

We estimate approximately six months will be necessary from that time for

lead optimization and product candidate nomination.

From lead candidate nomination, we anticipate approximately 12 months to perform

IND enabling studies and submit an IND for First in Human studies.

Development of the program could potentially be accelerated

with additional resources.

We initiated development of a series of

compounds that exhibit potent PDE10 inhibition and induce degradation of β-catenin to suppress key proteins essential for

tumor cell proliferation and survival.

Initial plans for continued preclinical development will be funded with ADT using SBIR

grants to ADT.

While we are excited by the potential for this program, we have made the decision to initially prioritize advancement

of our pan-RAS program.

Once a product candidate has been nominated for IND-enabling studies in the pan-RAS program, we plan to

allocate resources for development of the PDE10/ β-catenin program.

We estimate approximately six months will be necessary

from that time for lead optimization and product candidate nomination.

From lead candidate nomination, we anticipate approximately

12 months to perform IND enabling studies and submit an IND for First in Human studies.

Development of the program could potentially

be accelerated with additional resources.

Clinical Development Plan and Regulatory Pathway

Clinical development will be initiated once

a lead product candidate has been nominated, all necessary Investigational New Drug (IND) enabling studies have been performed

Clinical development will be initiated

once a lead product candidate has been nominated, all necessary Investigational New Drug (IND) enabling studies have been performed

and an IND application has been successfully submitted to and accepted by the USA.

Initial Phase 1 clinical investigation in cancer

will be performed in patients with advanced solid tumors, focusing on tumor types where the Wnt/APC/β-catenin pathway is implicated

such as colorectal cancer, hepatocellular carcinoma, breast cancer and lung cancer, with the objective of identifying a recommended

Phase 2 dose and to evaluate the safety and tolerability of the product candidate, as well as to evaluate preliminary anti-tumor

We anticipate that colorectal cancer may be an initial indication of focus in pivotal development, given the prominence

of the Wnt/APC/β-catenin pathway in this disease.

Subsequent development will be dependent on the signs of activity observed.

will be performed in patients with advanced solid tumors, focusing on tumor types where the Wnt/APC/β-catenin pathway is

implicated such as colorectal cancer, hepatocellular carcinoma, breast cancer and lung cancer, with the objective of identifying

a recommended Phase 2 dose and to evaluate the safety and tolerability of the product candidate, as well as to evaluate preliminary

anti-tumor activity.

We anticipate that colorectal cancer may be an initial indication of focus in pivotal development, given

the prominence of the Wnt/APC/β-catenin pathway in this disease.

Subsequent development will be dependent on the signs of

activity observed.

If efficacy data allows (i.e.

high response rate with meaningful duration of response in an indication of high unmet need), an

accelerated approval path based on Phase 2 data may be considered.

If not, a more traditional approach with a randomized Phase

3 program comparing to standard of care treatment will be required.

development path in FAP may also be pursued.

This would initiate with a Phase 1 dose escalation study in healthy volunteers (single

dose) and FAP patients (multiple dose).

high response rate with meaningful duration of response in an indication of high

unmet need), an accelerated approval path based on Phase 2 data may be considered.

If not, a more traditional approach with a

randomized Phase 3 program comparing to standard of care treatment will be required.

A separate development path in FAP may

also be pursued.

This would initiate with a Phase 1 dose escalation study in healthy volunteers (single dose) and FAP patients

(multiple dose).

A randomized Phase 3 program in patients with FAP is anticipated to be required for registration.

As mentioned above,

in light of business circumstances, and in order to conserve cash and preserve optionality while alternatives are being identified

and assessed, we made a decision during July 2020 to undertake reductions in headcount and other cost saving measures.

included plans to temporarily reduce our internal and external research and development work on the Company’s PDE10/β-catenin

Programs until there is greater clarity regarding Anchiano’s ability to fund the program.

We continue to undertake actions

for the promotion of the program and its assets and towards strengthening the protection of all related intellectual property.

Collaborations and License Agreements

2019, we entered into the Collaboration Agreement with ADT pursuant to which we agreed to use commercially reasonable efforts to

conduct research and development activities with respect to the pan-RAS and PDE10/β-catenin programs under the oversight of

a steering committee jointly established with ADT.

ADT is a private company focused on discovering, developing and securing patent

protection for novel molecules that inhibit activated RAS- or Wnt-mediated signaling pathways that drive the growth of many human

ADT’s technology currently comprises a broad, novel proprietary small-molecule class, encompassing at least two

distinct mechanistic subclasses that share a common chemical core;

one subclass targets RAS and the other subclass inhibits PDE10

to activate cGMP/PKG signaling and induce degradation of the oncogenic pool of β-catenin.

the terms of the Collaboration Agreement, we were granted an exclusive option to license the RAS and PDE10/β-catenin programs

in exchange for a $3.0 million upfront payment to ADT and will fund certain research activities.

At any time through obtaining

an IND designation, we will have the option to exclusively license the compounds we develop worldwide and will be responsible for

all aspects of preclinical and clinical development and global commercialization.

If we exercise our option, we will pay ADT an

option exercise fee and will be responsible for development and commercialization of any compounds or products containing any compounds

under the pan-RAS and PDE10/ß-catenin programs.

We will also incur additional payment obligations to ADT for any product

candidates developed under the pan-RAS and PDE10/ß-catenin programs, including milestone payments based on certain events

with respect to product development and regulatory achievements, and royalty payments based on net sales of any commercialized

We are responsible for all aspects of development for the pan-RAS and PDE10/ß-catenin programs.

We also have the

option to sublicense the licenses granted to us by ADT.

In connection

with the Collaboration Agreement, we also entered into a Consulting and Collaboration Research Support Agreement with ADT (the

“Support Agreement”), whereby ADT provides support services for our research and development activities with respect

to the pan-RAS and PDE10/ß-catenin programs, including providing key research and discovery personnel, in exchange for a

terminate the Collaboration Agreement in the event of a material default in any of our material obligations under the Collaboration

Agreement (following a cure period).

In the event the Collaboration Agreement is terminated, all licenses and options granted to

us will be terminated and we will not be able to develop the compounds under the pan-RAS and PDE10/ß-catenin programs or

any products containing such compounds.

The Collaboration Agreement also restricts assignment except to a successor of substantially

all of the business to which the Collaboration Agreement relates, whether in a merger, sale of stock, sale of assets, reorganization

or other transaction.

On November 14, 2005, we entered into a

license agreement with Yissum, which was subsequently amended several times, most recently in November 2013.

Yissum has granted

In September 2019, we entered into

the Collaboration Agreement with ADT pursuant to which we agreed to use commercially reasonable efforts to conduct research and

development activities with respect to the pan-RAS and PDE10/β-catenin programs under the oversight of a steering committee

jointly established with ADT.

ADT is a private company focused on discovering, developing and securing patent protection for novel

molecules that inhibit activated RAS- or Wnt-mediated signaling pathways that drive the growth of many human cancers.

technology currently comprises a broad, novel proprietary small-molecule class, encompassing at least two distinct mechanistic

subclasses that share a common chemical core;

one subclass targets RAS and the other subclass inhibits PDE10 to activate cGMP/PKG

signaling and induce degradation of the oncogenic pool of β-catenin.

Under the terms of the Collaboration Agreement,

we were granted an exclusive option to license the RAS and PDE10/β-catenin programs in exchange for a $3.0 million upfront

payment to ADT and will fund certain research activities.

At any time through obtaining an IND designation, we will have the option

to exclusively license the compounds we develop worldwide and will be responsible for all aspects of preclinical and clinical

development and global commercialization.

If we exercise our option, we will pay ADT an option exercise fee and will be responsible

for development and commercialization of any compounds or products containing any compounds under the pan-RAS and PDE10/ß-catenin

We will also incur additional payment obligations to ADT for any product candidates developed under the pan-RAS and

PDE10/ß-catenin programs, including milestone payments based on certain events with respect to product development and regulatory

achievements, and royalty payments based on net sales of any commercialized products.

We are responsible for all aspects of development

for the pan-RAS and PDE10/ß-catenin programs.

We also have the option to sublicense the licenses granted to us by ADT.

In connection with the Collaboration Agreement,

we also entered into a Consulting and Collaboration Research Support Agreement with ADT (the “Support Agreement”),

whereby ADT provides support services for our research and development activities with respect to the pan-RAS and PDE10/ß-catenin

programs, including providing key research and discovery personnel, in exchange for a fee.

ADT may terminate the Collaboration Agreement

in the event of a material default in any of our material obligations under the Collaboration Agreement (following a cure period).

In the event the Collaboration Agreement is terminated, all licenses and options granted to us will be terminated and we will

not be able to develop the compounds under the pan-RAS and PDE10/ß-catenin programs or any products containing such compounds.

The Collaboration Agreement also restricts assignment except to a successor of substantially all of the business to which the

Collaboration Agreement relates, whether in a merger, sale of stock, sale of assets, reorganization or other transaction.

On November 14, 2005, we entered into

the License Agreement with Yissum, which was subsequently amended several times, most recently in November 2013.

Yissum granted

us an exclusive, worldwide license for the development, use, manufacture and commercialization of products arising out of patents

owned by, and patent applications filed by Yissum in connection with the H19 and IGF2-P4 genes.

Yissum retains right, title and

Yissum retained right, title and

interest in the products, technologies or other inventions arising out of our research and development of these patents and patent

applications, except for intellectual property developed with funding from the Israel Innovation Authority (“IIA”),

which will be owned by us and transferred to Yissum only upon our dissolution or upon a decision by the IIA that it no longer requires

us to own the intellectual property developed with its funding.

We have the right to grant sub-licenses to third parties in accordance

with the terms set forth in the Yissum license agreement.

We have agreed to pay Yissum 4% of all “net

as royalties and 10% of the income that we receive from granting sub-licenses to third parties.

We will pay half of

these royalties on sales in countries in which no patent has been granted and a third party is selling identical products.

We are required to indemnify Yissum, the

Hebrew University of Jerusalem, their employees, directors, officers, representatives and any other persons acting on their behalf

under the license against any liability, including without limitation product liability, damages, losses or expenses, including

reasonable legal fees and litigation expenses arising out of our actions or omissions in performing the Yissum license, including

the use, development and manufacturing of patents arising out of it and the granting of sub-licenses thereunder, provided that

any such loss was not caused by the intentional misconduct or gross negligence of the indemnitees.

We have the right to terminate the Yissum

license upon three months’

prior written notice provided that we have paid all amounts owing to Yissum under the license.

Yissum has the right to terminate the license in the event that we become bankrupt, liquidated or insolvent, or if our business

is placed in the hands of a receiver, liquidator, or trustee.

In addition, Yissum has the right to terminate the license for any

material breach of it by us in the event that we fail to remedy such material breach within ninety days of Yissum’s notice

of our material breach, provided that the material breach is curable within 90 days.

In the event that the material breach cannot

be remedied within ninety days, Yissum may not terminate the license if we take reasonable commercial action to cure such breach

as promptly as practicable.

The termination of the license also entails termination of all licenses granted thereunder.

Any termination

of the license shall not terminate any of our obligations, including our obligation to pay royalties that matured prior to the

effective date of termination.

In November 2019, we discontinued the pivotal

Phase 2 Codex study, evaluating the gene therapy inodiftagene in patients with BCG-unresponsive NMIBC.

After a thorough analysis

of the data, we determined that there was a low probability of surpassing the pre-defined futility threshold at the planned interim

analysis, which required 10 complete responses in 35 patients.

At the time we discontinued the study, 16 patients were evaluable

after the first disease assessment on treatment, of which three patients, or 19%, had experienced a complete response.

also indicated a low probability of achieving an efficacy profile that in the company’s estimation would be necessary to

support regulatory approval.

which will be owned by us and transferred to Yissum only upon our dissolution or termination of the License Agreement or upon

a decision by the IIA that it no longer requires us to own the intellectual property developed with its funding.

We have the right

to grant sub-licenses to third parties in accordance with the terms set forth in the License Agreement.

In November 2019, we discontinued

the pivotal Phase 2 Codex study, evaluating the gene therapy inodiftagene in patients with BCG-unresponsive NMIBC.

After a thorough

analysis of the data, we determined that there was a low probability of surpassing the pre-defined futility threshold at the planned

interim analysis, which required 10 complete responses in 35 patients.

At the time we discontinued the study, 16 patients were

evaluable after the first disease assessment on treatment, of which three patients, or 19%, had experienced a complete response.

The data also indicated a low probability of achieving an efficacy profile that in the company’s estimation would be necessary

to support regulatory approval.

The safety data on the investigational product were consistent with those observed in prior trials.

While no further clinical development is currently planned, we maintain rights on inodiftagene and may evaluate out-licensing or

partnering opportunities with the therapy including other NMIBC on oncology indications, subject to terms of the Yissum agreement.

In April 2020 we notified Yissum that

as a result of our decision to discontinue clinical development of inodiftagene, we will cease payments to maintain intellectual

property (“IP”) we licensed from Yissum that supported the development and as related to the License Agreement.

August 2020 we agreed with Yissum on termination of the License Agreement, we destroyed or returned all IP documentation

to Yissum, and Yissum and we mutually waived, released and discharged the other from all claims of any type.

Our Competitive Strengths

2 unchanged sentences

of human cancer, the RAS pathway and the Wnt/APC/β-catenin biochemical pathway.

We are initially focusing on our pan-RAS program,

and we are developing compounds that exhibit pan-RAS cytotoxicity.

We are initially focusing on our pan-RAS

program, and we are developing compounds that exhibit pan-RAS cytotoxicity.

We believe we can develop these compounds

2 unchanged sentences

Our product candidates are targeted therapies.

We believe that the application of small molecule targeted therapy

approaches to pan-RAS inhibition has a high likelihood of success.

The development of small molecule targeted therapies against

the products of mutated driver oncogenes is one of the most productive endeavors in the field of cancer therapy.

Mutated driver

oncogenes cause cancer cell proliferation, the first and most fundamental hallmark of cancer.

The RAS genes are the most common

example of such mutated driver oncogenes.

These cancer genes have been identified by natural selection as being critical drivers

of malignant proliferation and they are prime therapeutic targets.

This potential for therapeutic exploitation has in turn been

coupled with progress in physical methods and chemical engineering that allow the design of small molecules that directly inhibit

the function of the key mutated driver genes.

This approach has resulted in successful therapies for cancers whose genetic alterations

include mutations in a variety of oncogenes.

An important observation from this field is that, in general, preclinical data, both

in vitro and in vivo , have been very strongly predictive for the development of these therapies.

If the physical

inhibition of the target molecule can be established and characterized by structural, chemical and biochemical methods and the

target gene is a mutated positively acting driver gene, then preclinical activity correlates strongly with clinical activity.

We believe that the application of small molecule targeted therapy approaches to pan-RAS inhibition has a high

likelihood of success.

The development of small molecule targeted therapies against the products of mutated driver oncogenes

is one of the most productive endeavors in the field of cancer therapy.

Mutated driver oncogenes cause cancer cell proliferation,

the first and most fundamental hallmark of cancer.

The RAS genes are the most common example of such mutated driver oncogenes.

These cancer genes have been identified by natural selection as being critical drivers of malignant proliferation and they

are prime therapeutic targets.

This potential for therapeutic exploitation has in turn been coupled with progress in physical

methods and chemical engineering that allow the design of small molecules that directly inhibit the function of the key mutated

driver genes.

This approach has resulted in successful therapies for cancers whose genetic alterations include mutations in

a variety of oncogenes.

An important observation from this field is that, in general, preclinical data, both in vitro

and in vivo , have been very strongly predictive for the development of these therapies.

If the physical inhibition

of the target molecule can be established and characterized by structural, chemical and biochemical methods and the target

gene is a mutated positively acting driver gene, then preclinical activity correlates strongly with clinical activity.

RAS family of genes are driver oncogenes, the most commonly mutated oncogenes known.

We believe that our existing preclinical data

demonstrating and characterizing small molecule pan-RAS inhibition forms the foundation for development of these molecules into

product candidates that can be used in clinical settings.

We believe that our existing preclinical

data demonstrating and characterizing small molecule pan-RAS inhibition forms the foundation for development of these molecules

into product candidates that can be used in clinical settings.

Our molecules are first-in-class molecules.

There are no small molecule targeted therapies that have successfully

been shown to exhibit pan-RAS inhibitory activity, and whose mechanism of action involves direct inhibition of RAS.

approaches to RAS inhibition have been tested, including interference with the intracellular localization and processing of RAS,

inhibition of its binding to other signaling molecules, and other approaches.

Current clinical–stage investigational drugs,

such as AMG-510, have been shown to bind to and directly inhibit the KRAS G12C mutation, a subset of mutant RAS proteins.

is one of 3 RAS family genes, and approximately 9% of RAS mutations are KRAS G12C mutations.

To our knowledge, no other pan-RAS

inhibitors like our molecules are currently being tested.

Our preclinical data strongly support the activity of our molecules against cancer.

The characteristics one would

predict in molecules with preclinical pan-RAS inhibitory activity include:

There are no small molecule targeted therapies that have successfully been shown to exhibit pan-RAS inhibitory

activity, and whose mechanism of action involves direct inhibition of RAS.

A variety of approaches to RAS inhibition have

been tested, including interference with the intracellular localization and processing of RAS, inhibition of its binding to

other signaling molecules, and other approaches.

Current clinical–stage investigational drugs, such as AMG-510, have

been shown to bind to and directly inhibit the KRAS G12C mutation, a subset of mutant RAS proteins.

KRAS is one of 3 RAS family

genes, and approximately 9% of RAS mutations are KRAS G12C mutations.

To our knowledge, no other pan-RAS inhibitors like our

molecules are currently being tested.

Our preclinical data strongly support

the activity of our molecules against cancer.

The characteristics one would predict in molecules with preclinical

pan-RAS inhibitory activity include:

selectivity for activated RAS;

nanomolar potency against

cells harboring mutant RAS;

nanomolar potency against cells harboring mutant RAS;

consistency of biochemical data with RAS inhibition (as opposed to other pathway points of inhibition);

evidence for binding RAS directly;

evidence for binding

RAS directly;

in vivo anti-tumor activity;

and immunological stimulation in vivo consistent

with other clinical RAS inhibitors.

Our small molecule inhibitors have been demonstrated to have these characteristics, and we

believe we can develop our molecules into product candidates that will have potential for pan-RAS inhibition in a variety of clinical

Recent data have validated cancer treatment with a RAS inhibitor.

Until recently, the unique biochemistry and

biology of the RAS gene family had resisted efforts of cancer biologists to discover and develop drugs capable of inhibiting the

activity of the mutated protein.

However, recent developments have led to the discovery of small molecules capable of inhibiting

a particular mutated form of RAS, known as KRAS G12C.

Preliminary successes of drugs under development such as AMG-510 and MRTX849,

are field-altering, as for the first time there is evidence that inhibition of mutated RAS isoforms may be undertaken in the same

manner as other successful small molecule targeted therapies had shown possible against other mutated oncogenes.

In other words,

RAS is a clinically validated target susceptible to small-molecule targeted therapy approaches.

Our development plan addresses substantial unmet needs.

Despite the preliminary success demonstrated by AMG 510

and MRTX849, KRAS is only one of three mutated isoforms of the RAS gene family, comprising approximately 85% of RAS mutations,

and only approximately 11% of KRAS mutations are of the G12C type.

A number of tumor types have large proportions of mutations

in other RAS isoforms.

Melanoma exhibits mutations in RAS in approximately 30% of cases, almost all of which are in NRAS.

55% of colorectal cancers that carry RAS mutations, 5% are NRAS.

Approximately half of the mutations in multiple myeloma are in

The RAS mutations in thyroid cancer and acute myeloid leukemia are predominantly NRAS (approximately 5-15% (depending on

sub-type) and 15% respectively) .

and immunological stimulation in vivo consistent with other clinical

RAS inhibitors.

Our small molecule inhibitors have been demonstrated to have these characteristics, and we believe we can

develop our molecules into product candidates that will have potential for pan-RAS inhibition in a variety of clinical settings.

Recent data have validated cancer treatment

with a RAS inhibitor.

Until recently, the unique biochemistry and biology of the RAS gene family had resisted

efforts of cancer biologists to discover and develop drugs capable of inhibiting the activity of the mutated protein.

recent developments have led to the discovery of small molecules capable of inhibiting a particular mutated form of RAS, known

as KRAS G12C.

Preliminary successes of drugs under development such as AMG-510 and MRTX849, are field-altering, as for the

first time there is evidence that inhibition of mutated RAS isoforms may be undertaken in the same manner as other successful

small molecule targeted therapies had shown possible against other mutated oncogenes.

In other words, RAS is a clinically

validated target susceptible to small-molecule targeted therapy approaches.

Our development plan addresses substantial

Despite the preliminary success demonstrated by AMG 510 and MRTX849, KRAS is only one of three

mutated isoforms of the RAS gene family, comprising approximately 85% of RAS mutations, and only approximately 11% of KRAS

mutations are of the G12C type.

A number of tumor types have large proportions of mutations in other RAS isoforms.

exhibits mutations in RAS in approximately 30% of cases, almost all of which are in NRAS.

Of the 55% of colorectal cancers

that carry RAS mutations, 5% are NRAS.

Approximately half of the mutations in multiple myeloma are in NRAS.

The RAS mutations

in thyroid cancer and acute myeloid leukemia are predominantly NRAS (approximately 5-15% (depending on sub-type) and 15% respectively)

Bladder and head and neck cancers carry largely HRAS mutations.

This means that while recent

observations have proven that RAS-directed therapy using small molecule inhibitors is possible with clinical effect, results so

far are confined to a small subset of patients carrying a particular mutation.

In a larger sense, even though preliminary success

has been demonstrated by KRAS G12C mutation inhibitors, at this time there are no approved inhibitors of mutated RAS in cancers

that carry these genetic lesions.

We believe there is much potential for broader treatment of RAS-mutated tumors, for treatment

of tumors that have become resistant after KRAS G12C mutation-inhibitor therapy, for earlier line treatment and for combination

therapy, and we believe that we can develop our molecules into product candidates capable of potentially meeting these broader

We have experienced and accomplished leadership with a history of successful drug development and U.S.

and international

approvals in the small molecule targeted therapy fields.

Our management team has a long track record of developing small

molecule targeted therapy.

Our CEO was part of the team that first discovered mutations in EGFR, and ran a laboratory at Massachusetts

General Hospital funded by the National Cancer Institute (the “NCI”) investigating BRAF signaling in melanoma.

at ARIAD Pharmaceuticals, he and our present clinical development team led the development and approval efforts of ponatinib (marketed

as Iclusig) for leukemia, and initiated the studies that were the foundation of the approval of brigatinib (marketed as Alunbrig).

Those studies were consummated by our CMO, who led the approval of Alunbrig for ALK-driven lung cancer at Takeda Pharmaceuticals.

We believe our current management team has the right combination of experience, history of success, and vision to execute the proposed

This means that while recent observations have proven that

RAS-directed therapy using small molecule inhibitors is possible with clinical effect, results so far are confined to a small

subset of patients carrying a particular mutation.

In a larger sense, even though preliminary success has been demonstrated

by KRAS G12C mutation inhibitors, at this time there are no approved inhibitors of mutated RAS in cancers that carry these

genetic lesions.

We believe there is much potential for broader treatment of RAS-mutated tumors, for treatment of tumors that

have become resistant after KRAS G12C mutation-inhibitor therapy, for earlier line treatment and for combination therapy,

and we believe that we can develop our molecules into product candidates capable of potentially meeting these broader needs.

Intellectual Property

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Trade secrets and know-how can be difficult to protect.

We seek to protect our proprietary processes, in part, by confidentiality agreements and invention assignment agreements with our

employees, consultants, scientific advisors, contractors and commercial partners.

These agreements are designed to protect our

proprietary information.

We also seek to preserve the integrity and confidentiality of our data, trade secrets and know-how by

maintaining physical security of our premises and physical and electronic security of our information technology systems.

we have confidence in these individuals, organizations and systems, such agreements or security measures may be breached, and we

may not have adequate remedies for any breach.

In addition, our trade secrets may otherwise become known or be independently discovered

by competitors or others.

We seek to protect our proprietary processes, in part, by confidentiality agreements and invention assignment agreements with

our employees, consultants, scientific advisors, contractors and commercial partners.

These agreements are designed to protect

our proprietary information.

We also seek to preserve the integrity and confidentiality of our data, trade secrets and know-how

by maintaining physical security of our premises and physical and electronic security of our information technology systems.

we have confidence in these individuals, organizations and systems, such agreements or security measures may be breached, and

we may not have adequate remedies for any breach.

In addition, our trade secrets may otherwise become known or be independently

discovered by competitors or others.

Pan-RAS and PDE10/β-catenin Program Patents

Pursuant to the Collaboration Agreement,

we have been granted an exclusive option to license patent rights for our pan-RAS and PDE10/ b -catenin

to the Collaboration Agreement, we have been granted an exclusive option to license patent rights for our pan-RAS and PDE10/ b -catenin

This patent portfolio includes three issued U.S.

patents directed to RAS inhibitor compounds, prodrugs and methods of

use, together with two pending related U.S.

patent applications directed to RAS and PDE10 inhibitor compounds and corresponding

foreign pending counterpart patent applications, and one Patent Cooperation Treaty (“PCT”) patent application directed

to RAS inhibitor compounds.

The issued U.S.

patents, and pending U.S.

patents, 2 issued Japanese patents, and one issued patent in each of

China, Australia, Europe and Hong Kong directed to RAS inhibitor compounds, prodrugs and methods of use.

In addition to this we

have two pending related U.S.

patent applications directed to RAS and PDE10 inhibitor compounds and corresponding foreign pending

counterpart patent applications, and one Patent Cooperation Treaty (“PCT”) patent application directed to RAS inhibitor

The issued patents, and pending U.S.

patent applications, if issued, will expire in 2035.

any patents based on the PCT application, if we continue to pursue patent protection in the United States and elsewhere, if issued,

to expire in 2039.

Inodiftagene Program Patents

Pursuant to a license agreement with Yissum,

described above, we also have an exclusive, worldwide license for the development, use, manufacture and commercialization of products

arising out of patents owned by, and patent applications filed by, Yissum in connection with our inodiftagene program and our additional

technologies as described below.

Our licensed inodiftagene patent portfolio

includes one pending U.S.

patent application directed to formulations of inodiftagene.

and corresponding pending foreign patent

applications.

If issued, we expect these patent applications to expire in 2036.

Patents on the original active formulation of our

lead product candidate, inodiftagene, expired during 2017 and 2018.

We expect any patents based

on the PCT application, if we continue to pursue patent protection in the United States and elsewhere, if issued, to expire in

Additional Technologies

BC-821  - Our licensed patent portfolio includes two issued U.S.

patents directed to composition of matter

and method of use, and related issued foreign patents and patent applications.

We expect these patents and patent application,

if issued, to expire between 2028 and 2029.

BC-821  - Our licensed

patent portfolio includes two issued U.S.

patents directed to composition of matter and method of use, and related issued

foreign patents and patent applications.

We expect these patents and patent application, if issued, to expire between 2028

Cancer-Specific TNF-α

and DTA mutual expression vector  - Our licensed patent portfolio includes

patent directed to nucleic acid vectors and related issued foreign patents.

and DTA mutual

expression vector  - Our licensed patent portfolio includes one U.S.

patent directed to nucleic acid

vectors and related issued foreign patents.

We expect these patents to expire in 2026.

H19 targeted siRNA for cancer  - Our licensed patent portfolio includes one issued U.S.

patent directed

to composition of matter, and related foreign patents.

H19 targeted siRNA for cancer  - Our

licensed patent portfolio includes one issued U.S.

patent directed to composition of matter, and related foreign patents.

We expect these patents to expire in 2026.

H19 targeted siRNA for rheumatoid arthritis  - Our licensed patents include one issued U.S.

patent directed to

methods for treating rheumatoid arthritis, and related foreign patents.

H19 targeted siRNA for rheumatoid arthritis  -

Our licensed patents include one issued U.S.

patent directed to methods for treating rheumatoid arthritis, and related foreign

We expect these patents to expire in 2028.

Marketing, Sales and Distribution

our stage of development, we do not have any internal sales, marketing or distribution infrastructure or capabilities.

we receive regulatory approval for a future product candidate and secure adequate funding, we intend, where appropriate, to consider

commercialization relationships.

In addition, we may consider out-licensing some or all of our worldwide patent rights to more

than one party to achieve the fullest development, marketing and distribution of any future product we develop.

Given our stage of development, we do not

have any internal sales, marketing or distribution infrastructure or capabilities.

In the event we receive regulatory approval

for a future product candidate and secure adequate funding, we intend, where appropriate, to consider commercialization relationships.

In addition, we may consider out-licensing some or all of our worldwide patent rights to more than one party to achieve the fullest

development, marketing and distribution of any future product we develop.

Competition in the development of human

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We believe our primary competitors by program and target are as follows:

Pan-RAS Program :

aware of any competitors with development programs or molecules in clinical testing that target mutations across all three RAS

family of genes (HRAS, KRAS, and NRAS).

We are aware of several competitors with clinical and preclinical development programs

that directly target one or more mutations in KRAS family of genes, including Mirati Therapeutics, Inc., Amgen, Inc., Boehringer

Ingelheim AG, Merck & Co., Inc., and others.

It is likely that other companies are also researching inhibitors in the HRAS

and NRAS families of genes.

We will continue to monitor scientific and patent publications for the emergence of other potential

PDE10/β-catenin Program :

We are aware of several companies that have PDE10 inhibitor programs in preclinical or clinical development, including among others,

We are not aware of any competitors with development programs or molecules in clinical testing that target

mutations across all three RAS family of genes (HRAS, KRAS, and NRAS).

We are aware of several competitors with clinical and preclinical

development programs that directly target one or more mutations in KRAS family of genes, including Mirati Therapeutics, Inc.,

Amgen, Inc., Boehringer Ingelheim AG, Merck & Co., Inc., and others.

It is likely that other companies are

also researching inhibitors in the HRAS and NRAS families of genes.

We will continue to monitor scientific and patent publications

for the emergence of other potential competitors.

PDE10/β-catenin

We are aware of several companies that have PDE10 inhibitor programs in preclinical or clinical development,

including among others, H.

Lundbeck A/S, Omeros Corporation, and Celon Pharma SA –mainly focused on CNS indications.

Likewise, we are aware of several

companies that have β-catenin inhibitor program in preclinical or clinical development, including among others, PRISM Pharma

Co., Ltd, and Fog Pharmaceuticals, Inc.

We will continue to monitor scientific and patent publications for the emergence of other

potential competitors.

we are aware of several companies that have β-catenin inhibitor program in preclinical or clinical development, including

among others, PRISM Pharma Co., Ltd, and Fog Pharmaceuticals, Inc.

We will continue to monitor scientific and patent publications

for the emergence of other potential competitors.

Government Regulation

We are subject to extensive regulation by

the various national health regulatory authorities, such as the FDA, Health Canada and other national, state and provincial regulatory

We are subject to extensive regulation

by the various national health regulatory authorities, such as the FDA, Health Canada and other national, state and provincial

regulatory agencies.

Food and Drug Administration

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The marketing authorization

of our products would be conditional upon obtaining the approval of health authorities in each country in which they would be marketed,

including, but not limited to, the FDA and the EMA.

FDA regulations govern the following activities that we may perform, or that

have been performed on our behalf, to ensure that drugs that we develop are safe and effective for their intended uses:

preclinical (animal) testing including toxicology studies;

submission of an IND;

human testing in clinical trials, Phases 1, 2 and 3;

recordkeeping and retention;

pre-marketing review through submission of a new drug application (“NDA”);

drug manufacturing, testing and labeling, which must comply with current good manufacturing practice

(“cGMP”) regulations;

drug marketing, sales and distribution;

post-marketing study commitments (Phase 4), post-marketing pharmacovigilance surveillance, complaint

handling, reporting of deaths or serious injuries, product sample retention, manufacturing deviation reporting and repair or recall

Failure to comply with applicable regulatory

requirements can result in enforcement action by the FDA, which may include any of the following sanctions:

warning letters, untitled letters, fines, injunctions, consent decrees and civil penalties;

disqualification of clinical investigator and/or sponsor from current and future studies;

clinical hold on clinical trials;

operating restrictions, partial suspension or total shutdown of production;

refusal to approve an NDA;

post-marketing withdrawal of approval;

criminal prosecution.

of our products would be conditional upon obtaining the approval of health authorities in each country in which they would be

marketed, including, but not limited to, the FDA and the EMA.

FDA regulations govern the following activities that we may perform,

or that have been performed on our behalf, to ensure that drugs that we develop are safe and effective for their intended uses:

preclinical (animal)

testing including toxicology studies;

submission of an

human testing in

clinical trials, Phases 1, 2 and 3;

recordkeeping and

pre-marketing review

through submission of a new drug application (“NDA”);

drug manufacturing,

testing and labeling, which must comply with current good manufacturing practice (“cGMP”) regulations;

drug marketing,

sales and distribution;

post-marketing study

commitments (Phase 4), post-marketing pharmacovigilance surveillance, complaint handling, reporting of deaths or serious injuries,

product sample retention, manufacturing deviation reporting and repair or recall of drugs.

Failure to comply with

applicable regulatory requirements can result in enforcement action by the FDA, which may include any of the following sanctions:

warning letters,

untitled letters, fines, injunctions, consent decrees and civil penalties;

disqualification

of clinical investigator and/or sponsor from current and future studies;

clinical hold on

clinical trials;

operating restrictions,

partial suspension or total shutdown of production;

refusal to approve

post-marketing withdrawal

The FDA’s preclinical and IND requirements

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an IND can be prepared and submitted to the FDA for review.

In the IND review process, FDA physicians and scientists evaluate the

proposed clinical trial protocol, chemistry and manufacturing controls, pharmacologic mechanisms of action of the drug and toxicological

effects of the drug in animals and in vitro .

Within 30 days of the IND submission, the drug review division of the FDA may

contact the filer regarding potential concerns and, if necessary, implement a clinical hold until certain issues are resolved satisfactorily.

In the IND review process, FDA physicians and scientists evaluate

the proposed clinical trial protocol, chemistry and manufacturing controls, pharmacologic mechanisms of action of the drug and

toxicological effects of the drug in animals and in vitro .

Within 30 days of the IND submission, the drug review division

of the FDA may contact the filer regarding potential concerns and, if necessary, implement a clinical hold until certain issues

are resolved satisfactorily.

If the FDA does not take any action, the filer may proceed with clinical trials on the 31st day.

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The application includes all relevant data available from pertinent preclinical and clinical trials, including negative

or ambiguous results as well as positive findings, together with detailed information relating to the drug’s chemistry, manufacturing,

controls and proposed labeling, among other things.

In most cases, the

submission of an NDA is subject to a substantial application fee.

FDA has 60 days from its receipt of an NDA to determine whether the application will be accepted for filing based on the agency’s

threshold determination that it is sufficiently complete to permit substantive review.

Once the NDA submission is accepted for

filing, the FDA begins an in-depth substantive review.

or ambiguous results as well as positive findings, together with detailed information relating to the drug’s chemistry,

manufacturing, controls and proposed labeling, among other things.

In most cases, the submission of an NDA is subject to a substantial

application fee.

The FDA has 60 days from its receipt of

an NDA to determine whether the application will be accepted for filing based on the agency’s threshold determination that

it is sufficiently complete to permit substantive review.

Once the NDA submission is accepted for filing, the FDA begins an in-depth

substantive review.

NDAs receive either standard or priority review.

FDA has a goal of ten months from the date of filing to review and act on a standard NDA for a new molecular entity.

representing a significant improvement over existing therapy in the treatment, prevention or diagnosis of a disease may receive

priority review.

The FDA has various specific programs, including

Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review, each of which is intended to expedite the process for

reviewing drugs, and in certain cases involving Accelerated Review, permit approval of a drug on the basis of a surrogate endpoint.

Even if a drug qualifies for one or more of these programs, the FDA may later decide that the drug no longer meets the conditions

for qualification or that the time period for FDA review or approval will be shortened.

Fast Track designation facilitates the

development and expedites the review of drugs to treat serious or life-threatening diseases or conditions and fill unmet medical

The FDA has a goal of ten months from the date of filing

to review and act on a standard NDA for a new molecular entity.

A drug representing a significant improvement over existing therapy

in the treatment, prevention or diagnosis of a disease may receive priority review.

The FDA has various specific programs,

including Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review, each of which is intended to expedite the

process for reviewing drugs, and in certain cases involving Accelerated Review, permit approval of a drug on the basis of a surrogate

Even if a drug qualifies for one or more of these programs, the FDA may later decide that the drug no longer meets the

conditions for qualification or that the time period for FDA review or approval will be shortened.

Fast Track designation facilitates

the development and expedites the review of drugs to treat serious or life-threatening diseases or conditions and fill unmet medical

Although this designation does not affect the standards for approval, the FDA will attempt to facilitate early and frequent

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committee for review, evaluation and recommendation as to whether the application should be approved.

The FDA is not bound by the

recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

The FDA is not bound by

the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Before approving an NDA, the FDA typically

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Pervasive and continuing regulation in the United States

After a drug is approved for marketing and

enters the marketplace, numerous regulatory requirements continue to apply.

After a drug is approved for marketing

and enters the marketplace, numerous regulatory requirements continue to apply.

These include, but are not limited to:

The FDA’s cGMP regulations require manufacturers, including third-party manufacturers, to

follow stringent requirements for the methods, facilities and controls used in manufacturing, processing, testing and packing of

a drug product;

Labeling regulations and the FDA prohibitions against the promotion of drug for unapproved uses

(known as off-label uses), as well as requirements to provide adequate information on both risks and benefits during promotion

Approval of product modifications or use of the drug for an indication other than approved in the

Adverse drug experience regulations, which require companies to report information on rare, latent

or long-term drug effects not identified during pre-market testing;

Post-market testing and surveillance requirements, including Phase 4 trials, when necessary, to

protect the public health or to provide additional safety and effectiveness data for the drug;

The FDA’s recall authority, whereby it can ask, or under certain conditions order, drug manufacturers

to recall from the market a product that is in violation of governing laws and regulations.

FDA’s cGMP regulations require manufacturers, including third-party manufacturers, to follow stringent requirements

for the methods, facilities and controls used in manufacturing, processing, testing and packing of a drug product;

regulations and the FDA prohibitions against the promotion of drug for unapproved uses (known as off-label uses), as well

as requirements to provide adequate information on both risks and benefits during promotion of the drug;

of product modifications or use of the drug for an indication other than approved in the NDA;

drug experience regulations, which require companies to report information on rare, latent or long-term drug effects not identified

during pre-market testing;

testing and surveillance requirements, including Phase 4 trials, when necessary, to protect the public health or to provide

additional safety and effectiveness data for the drug;

FDA’s recall authority, whereby it can ask, or under certain conditions order, drug manufacturers to recall from the

market a product that is in violation of governing laws and regulations.

After a drug receives approval, any modification

in conditions of use, active ingredient(s), route of administration, dosage form, strength or bioavailability, will require a new

clearance or approval, for which it may be possible to submit a supplemental NDA, referring to preclinical and certain clinical

in conditions of use, active ingredient(s), route of administration, dosage form, strength or bioavailability, will require a

new clearance or approval, for which it may be possible to submit a supplemental NDA, referring to preclinical and certain clinical

studies presented in the drug’s original NDA, accompanied by additional clinical data necessary to demonstrate the safety

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Federal Trade Commission and corresponding state agencies.

Some of these laws significantly restrict or prohibit certain types

of sales, marketing and promotional activities by drug manufacturers.

Violation of these laws may result in significant criminal,

civil and administrative penalties, including imprisonment of individuals, fines and penalties and exclusion or debarment from

United States federal and state healthcare and other programs.

Many private health insurance companies also prohibit payment to

entities that have been sanctioned, excluded or debarred by U.S.

Some of these laws significantly restrict or prohibit certain

types of sales, marketing and promotional activities by drug manufacturers.

Violation of these laws may result in significant

criminal, civil and administrative penalties, including imprisonment of individuals, fines and penalties and exclusion or debarment

from United States federal and state healthcare and other programs.

Many private health insurance companies also prohibit payment

to entities that have been sanctioned, excluded or debarred by U.S.

federal agencies.

Anti-kickback statutes in the United States

federal anti-kickback statute prohibits,

among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or

indirectly, in exchange for or to induce either the referral of an individual, or the furnishing, arranging for or recommending

of a good or service, for which payment may be made in whole or in part under a United States federal healthcare program such as

the Medicare and Medicaid programs.

federal anti-kickback statute

prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration,

directly or indirectly, in exchange for or to induce either the referral of an individual, or the furnishing, arranging for or

recommending of a good or service, for which payment may be made in whole or in part under a United States federal healthcare

program such as the Medicare and Medicaid programs.

The definition of “remuneration”

has been broadly interpreted to include anything

of value, including gifts, discounts, the furnishing of supplies or equipment, payments of cash and waivers of payments.

courts have interpreted the statute’s intent requirement to mean that, if any one purpose of an arrangement involving remuneration

is to induce referrals or otherwise generate business involving goods or services reimbursed in whole or in part under federal

healthcare programs, the statute has been violated.

Penalties for violations include criminal penalties and civil sanctions such

as fines, imprisonment and possible exclusion from Medicare, Medicaid and other U.S.

federal healthcare programs.

some kickback allegations have been claimed to violate the U.S.

has been broadly interpreted

to include anything of value, including gifts, discounts, the furnishing of supplies or equipment, payments of cash and waivers

Several courts have interpreted the statute’s intent requirement to mean that, if any one purpose of an arrangement

involving remuneration is to induce referrals or otherwise generate business involving goods or services reimbursed in whole or

in part under federal healthcare programs, the statute has been violated.

Penalties for violations include criminal penalties

and civil sanctions such as fines, imprisonment and possible exclusion from Medicare, Medicaid and other U.S.

federal healthcare

In addition, some kickback allegations have been claimed to violate the U.S.

False Claims Act (as discussed below).

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Some of these state prohibitions are broader than the U.S.

federal statute, and apply to

the referral of patients and recommendations for healthcare items or services reimbursed by any source, not only the Medicare and

Medicaid programs.

federal statute, and apply

to the referral of patients and recommendations for healthcare items or services reimbursed by any source, not only the Medicare

and Medicaid programs.

Government officials have focused certain enforcement efforts on marketing of healthcare items and services,

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False Claims Act prohibits any

person from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment by a federal healthcare program

or knowingly making, or causing to be made, a false statement or record in order to have a false claim paid or avoiding, decreasing

or concealing an obligation to pay money to the federal government.

The federal government’s interpretation of the scope

of the law has in recent years grown increasingly broad.

Most states also have statutes or regulations similar to the U.S.

Claims Act, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply

regardless of the payor.

Sanctions under these federal and state laws may include civil monetary penalties, exclusion of a manufacturer’s

products from reimbursement under government programs, criminal fines and imprisonment.

Several drug manufacturers have been prosecuted

under the false claims laws for allegedly providing free drugs to physician customers with the expectation that the physician customers

would bill federal programs for the product.

In addition, several recent cases against drug manufacturers have alleged that the

manufacturers improperly promoted their products for “off-label”

use, outside of the scope of the FDA-approved labeling.

Health Insurance Portability and Accountability Act

of 1996 (HIPAA)

HIPAA created a new federal healthcare fraud

statute that prohibits knowingly and willfully executing a scheme to defraud any healthcare benefit program, including private

person from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment by a federal healthcare

program or knowingly making, or causing to be made, a false statement or record in order to have a false claim paid or avoiding,

decreasing or concealing an obligation to pay money to the federal government.

The federal government’s interpretation of

the scope of the law has in recent years grown increasingly broad.

Most states also have statutes or regulations similar to the

False Claims Act, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states,

apply regardless of the payor.

Sanctions under these federal and state laws may include civil monetary penalties, exclusion of

a manufacturer’s products from reimbursement under government programs, criminal fines and imprisonment.

Several drug manufacturers

have been prosecuted under the false claims laws for allegedly providing free drugs to physician customers with the expectation

that the physician customers would bill federal programs for the product.

In addition, several recent cases against drug manufacturers

have alleged that the manufacturers improperly promoted their products for “off-label”

use, outside of the scope of

the FDA-approved labeling.

Health Insurance Portability and Accountability

Act of 1996 (HIPAA)

HIPAA created a new federal healthcare

fraud statute that prohibits knowingly and willfully executing a scheme to defraud any healthcare benefit program, including private

A violation of this statute is a felony and may result in fines, imprisonment or exclusion from government-sponsored programs.

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a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment

for healthcare benefits, items or services, along with theft or embezzlement in connection with a healthcare benefits program and

willful obstruction of a criminal investigation involving a federal healthcare offense.

Affordable Care Act Section 6002 (the Sunshine Act)

for healthcare benefits, items or services, along with theft or embezzlement in connection with a healthcare benefits program

and willful obstruction of a criminal investigation involving a federal healthcare offense.

Further, HIPAA, as amended by the

Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations,

which also imposes certain obligations, including mandatory contractual terms, with respect to safeguarding the privacy and security

of individually identifiable health information of covered entities subject to the rule, such as health plans, healthcare clearinghouses

and certain healthcare providers as well as their business associates, independent contractors of a covered entity that perform

certain services involving the use or disclosure of individually identifiable health information on its behalf and their subcontractors

that use, disclose, access, or otherwise process individually identifiable health information.

Affordable Care Act Section 6002 (the Sunshine

Enacted in 2010 under the Affordable Care

Act of 2010, Public Law No.

111-148 (the “ACA”), the Sunshine Act is a national disclosure program that promotes transparency

by publishing data on the financial relationships between the healthcare industry (applicable manufacturers) and healthcare providers

(physicians and teaching hospitals) on a publicly accessible website.

The Sunshine Act requires that certain manufacturers of drugs,

devices, biologicals, or medical supplies report payments or other transfers of value made to physicians and teaching hospitals

111-148 (the “ACA”), the Physician Payments Sunshine Act is a national disclosure

program that promotes transparency by publishing data on the financial relationships between the healthcare industry (applicable

manufacturers) and healthcare providers (physicians and teaching hospitals) on a publicly accessible website.

The Sunshine Act

requires that certain manufacturers of drugs, devices, biologicals, or medical supplies report payments or other transfers of

value made to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors) and teaching hospitals

as well as certain ownership or investment interests held by physicians or their immediate family members to the Centers for Medicare &

Medicaid Services (CMS).

A violation of this act may result in fines and/or civil liabilities.

Any payment or transfer of

value that is currently prohibited under the anti-kickback statute, the U.S.

False Claims Act, or other health care fraud and abuse

laws may still be subject to fines, sanctions, or lawsuit.

Beginning in 2022, applicable manufacturers will also be required to report information regarding payments

and other transfers of value provided during the previous year to physician assistants, nurse practitioners, clinical nurse specialists,

certified nurse anesthetists, anesthesiologist assistants, and certified nurse-midwives.

A violation of this act may result in

fines and/or civil liabilities.

Any payment or transfer of value that is currently prohibited under the anti-kickback statute,

False Claims Act, or other health care fraud and abuse laws may still be subject to fines, sanctions, or lawsuit.

Marketing authorization requests outside

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(i) the “centralized”

procedure, described

in greater detail below, with applications made directly to the EMA leading to the grant of a European marketing authorization

described in greater detail below, with applications made directly to the EMA leading to the grant of a European marketing authorization

by the European Commission, (ii) the “decentralized procedure,”

whereby companies may apply for simultaneous authorization

in more than one EU country of medicinal products that have not yet been authorized in any EU country, or do not fall within the

mandatory scope of the centralized procedure, (iii) the “mutual recognition”

procedure, in which applications are made

to one or more member states, leading to national marketing authorizations mutually recognized by other member states, or (iv)

a “national authorization”

whereby companies may apply for simultaneous

authorization in more than one EU country of medicinal products that have not yet been authorized in any EU country, or do not

fall within the mandatory scope of the centralized procedure, (iii) the “mutual recognition”

procedure, in which

applications are made to one or more member states, leading to national marketing authorizations mutually recognized by other

member states, or (iv) a “national authorization”

application made to a single EU member state.

Based on the nature of our products, the marketing

authorization will be through the centralized procedure.

nature of our products, the marketing authorization will be through the centralized procedure.

The EMA is responsible for the centralized

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The procedure consists of three milestones:

(i) Evaluation by a scientific committee for up to seven months, at the end of which the committee

adopts an opinion on whether the drug should be approved for marketing.

During this period, the EMA may send questions to the company,

at which time the aforementioned review clock stops until answers are provided.

(ii) Formal decision by the EMA’s Committee for Medicinal Products for Human Use, which is transmitted

to the European Commission, which issues a formal decision on the authorization of the product.

(iii) Marketing authorization:

Once a European Community marketing authorization has been granted, the

marketing-authorization holder can begin to make the medicine available to patients and healthcare professionals in all EU countries.

by a scientific committee for up to seven months, at the end of which the committee adopts an opinion on whether the drug

should be approved for marketing.

During this period, the EMA may send questions to the company, at which time the aforementioned

review clock stops until answers are provided.

decision by the EMA’s Committee for Medicinal Products for Human Use, which is transmitted to the European Commission,

which issues a formal decision on the authorization of the product.

authorization:

Once a European Community marketing authorization has been granted, the marketing-authorization holder can

begin to make the medicine available to patients and healthcare professionals in all EU countries.

Even after a company receives marketing

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products for human use.

The European Union also regulates the manufacture of medicinal products, requiring cGMP, set forth in the

EU Guidelines to Good Manufacturing Practice —

The European Union also regulates the manufacture of medicinal products, requiring cGMP, set forth in

the EU Guidelines to Good Manufacturing Practice —

Medicinal Products for Human and Veterinary Use.

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A patent claiming a new drug product may

be eligible for a limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch-Waxman

Act”) which permits a patent restoration of up to five years for patent term lost during product development and FDA regulatory

The restoration period granted is typically one-half the time between the effective date of an IND and the submission date

of an NDA, plus the time between the submission date of an NDA and the ultimate approval date.

Patent term restoration cannot be

used to extend the remaining term of a patent past a total of 14 years from the product’s approval date.

Only one patent

applicable to an approved drug product is eligible for the extension, and the application for the extension must be submitted prior

to the expiration of the patent in question.

A patent that covers multiple drugs for which approval is sought can only be extended

in connection with one of the approvals.

The PTO reviews and approves the application for any patent term extension or restoration

in consultation with the FDA.

be eligible for a limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984 (the

“Hatch-Waxman Act”) which permits a patent restoration of up to five years for patent term lost during product development

and FDA regulatory review.

The restoration period granted is typically one-half the time between the effective date of an IND

and the submission date of an NDA, plus the time between the submission date of an NDA and the ultimate approval date.

term restoration cannot be used to extend the remaining term of a patent past a total of 14 years from the product’s approval

Only one patent applicable to an approved drug product is eligible for the extension, and the application for the extension

must be submitted prior to the expiration of the patent in question.

A patent that covers multiple drugs for which approval is

sought can only be extended in connection with one of the approvals.

The PTO reviews and approves the application for any patent

term extension or restoration in consultation with the FDA.

Pharmaceutical coverage, pricing and reimbursement

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not be considered medically necessary or cost-effective.

A payor’s decision to provide coverage for a drug product does not

imply that an adequate reimbursement rate will be approved.

Adequate third-party reimbursement may not be available to enable us

to maintain price levels sufficient to realize an appropriate return on our investment in product development.

A payor’s decision to provide coverage for a drug product does

not imply that an adequate reimbursement rate will be approved.

Adequate third-party reimbursement may not be available to enable

us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

In March 2010, a significant healthcare

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by both governmental and private insurers, and significantly impacts the pharmaceutical industry.

The comprehensive $940 billion

dollar overhaul is expected to extend coverage to approximately 32 million previously uninsured Americans.

The healthcare reform

law contains a number of provisions, including those governing enrollment in federal healthcare programs, reimbursement changes

and fraud and abuse, which will impact existing government healthcare programs and will result in the development of new programs,

including Medicare payment for performance initiatives and improvements to the physician quality reporting system and feedback

The healthcare reform law contains

a number of provisions, including those governing enrollment in federal healthcare programs, reimbursement changes and fraud and

abuse, which has impacted existing government healthcare programs and resulted in the development of new programs, including Medicare

payment for performance initiatives and improvements to the physician quality reporting system and feedback program.

Additionally, the healthcare reform law:

as limited by the United States Supreme Court’s decision in June 2012:

Increases the minimum level of Medicaid rebates payable by manufacturers of brand-name drugs from

15.1% to 23.1%;

Requires collection of rebates for drugs paid by Medicaid managed care organizations;

Imposes a non-deductible annual fee on pharmaceutical manufacturers or importers who sell “branded

prescription drugs”

the minimum level of Medicaid rebates payable by manufacturers of brand-name drugs from 15.1% to 23.1%;

collection of rebates for drugs paid by Medicaid managed care organizations;

a non-deductible annual fee on pharmaceutical manufacturers or importers who sell “branded prescription drugs”

to specified federal government programs.

There have been proposed in Congress a number

of legislative initiatives regarding healthcare, including possible repeal of the healthcare reform law.

At this time, it remains

unclear whether there will be any changes made to the healthcare reform law, whether to certain provisions or its entirety.

There have been executive, judicial and

Congressional challenges to certain aspects of the healthcare reform law.

Supreme Court is currently reviewing the constitutionality

of the healthcare reform law, although it is unknown when a decision will be made.

It is unclear how the Supreme Court ruling,

other such litigation, and the healthcare reform measures of the Biden administration will impact the healthcare reform law and

our business.

In addition, there has been increasing

legislative and enforcement interest in the United States with respect to drug pricing practices.

Specifically, there have been

several recent U.S.

Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things,

bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, and reform

government program reimbursement methodologies for drugs.

At the federal level, the Trump administration used several means to

propose or implement drug pricing reform, including through federal budget proposals, executive orders and policy initiatives.

It is unclear whether the Biden administration will work to reverse these measures or pursue similar policy initiatives.

additional healthcare reform initiatives to be adopted in the future, particularly in light of the new presidential administration.

We also expect these initiatives to increase pressure on drug pricing.

Further, it is possible that additional governmental action

is taken in response to the evolving effects of the COVID-19 pandemic.

In the European Union, pricing and reimbursement

schemes vary widely from country to country.

Some countries provide that drug products may be marketed only after agreeing on a

reimbursement price.

Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular

drug to currently available therapies.

For example, the European Union provides options for its member states to restrict the range

of drug products for which their national health insurance systems provide reimbursement and to control the prices of medicinal

products for human use.

European Union member states may approve a specific price for a drug product or may instead adopt a system

of direct or indirect controls on the profitability of the company placing the drug product on the market.

Other member states

allow companies to set their own prices for drug products, but monitor and control company profits.

The downward pressure on health

care costs in general, particularly prescription drugs, has become intense.

As a result, increasingly high barriers are being erected

to the entry of new products.

In addition, in some countries, cross-border imports from low-priced markets exert competitive pressure

that may reduce pricing within a country.

Any country that has price controls or reimbursement limitations for drug products may

not allow favorable reimbursement and pricing arrangements.

Some countries provide that drug products may be marketed only after agreeing on

a reimbursement price.

Some countries may require the completion of additional studies that compare the cost-effectiveness of

a particular drug to currently available therapies.

For example, the European Union provides options for its member states to

restrict the range of drug products for which their national health insurance systems provide reimbursement and to control the

prices of medicinal products for human use.

European Union member states may approve a specific price for a drug product or may

instead adopt a system of direct or indirect controls on the profitability of the company placing the drug product on the market.

Other member states allow companies to set their own prices for drug products, but monitor and control company profits.

pressure on health care costs in general, particularly prescription drugs, has become intense.

As a result, increasingly high

barriers are being erected to the entry of new products.

In addition, in some countries, cross-border imports from low-priced

markets exert competitive pressure that may reduce pricing within a country.

Any country that has price controls or reimbursement

limitations for drug products may not allow favorable reimbursement and pricing arrangements.

Environmental, Health and Safety Matters

agents and our service providers, including our manufacturers, may be subject to various environmental, health and safety laws

and regulations, including those governing air emissions, water and wastewater discharges, noise emissions, the use, management

and disposal of hazardous, radioactive and biological materials and wastes and the cleanup of contaminated sites.

We believe that

our business, operations and facilities, including, to our knowledge, those of our agents and service providers, are being operated

in compliance in all material respects with applicable environmental and health and safety laws and regulations.

All information

with respect to any chemical substance is filed and stored as a Material Safety Data Sheet, as required by applicable environmental

Based on information currently available to us, we do not expect environmental costs and contingencies to have a material

adverse effect on us.

However, significant expenditures could be required in the future if we, our agents or our service providers

are required to comply with new or more stringent environmental or health and safety laws, regulations or requirements.

As of December 31, 2019, we had 16 employees

based at our office and laboratory in Jerusalem, Israel and our Cambridge, Massachusetts office.

The following table sets forth

the total number of full-time employees as of the periods indicated by function and geography:

As of December 31,

We, our agents and our service providers,

including our manufacturers, may be subject to various environmental, health and safety laws and regulations, including those

governing air emissions, water and wastewater discharges, noise emissions, the use, management and disposal of hazardous, radioactive

and biological materials and wastes and the cleanup of contaminated sites.

We believe that our business, operations and facilities,

including, to our knowledge, those of our agents and service providers, are being operated in compliance in all material respects

with applicable environmental and health and safety laws and regulations.

All information with respect to any chemical substance

is filed and stored as a Material Safety Data Sheet, as required by applicable environmental regulations.

Based on information

currently available to us, we do not expect environmental costs and contingencies to have a material adverse effect on us.

significant expenditures could be required in the future if we, our agents or our service providers are required to comply with

new or more stringent environmental or health and safety laws, regulations or requirements.

As of December 31, 2020, we had 3

employees based in Jerusalem, Israel and our Cambridge, Massachusetts office.

The following table sets forth the total number

of full-time employees as of the periods indicated by function and geography:

of December 31,

Administrative

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Cambridge, Massachusetts, USA

In January 2020, our board of directors

approved management’s recommendation to close our office and laboratory in Israel.

Following the closure of our Israeli facilities,

our sole office will continue to be located in Cambridge, Massachusetts.

Local labor laws govern the length of the

workday and workweek, minimum wages for employees, procedures for hiring and dismissing employees, determination of severance pay,

annual leave, sick days, advance notice of termination, Social Security payments or regional equivalents, and other conditions

workday and workweek, minimum wages for employees, procedures for hiring and dismissing employees, determination of severance

pay, annual leave, sick days, advance notice of termination, Social Security payments or regional equivalents, and other conditions

of employment and include equal opportunity and anti-discrimination laws.

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The SEC maintains an internet site that

contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC.

contains reports, proxy and information statements, and other information regarding issuers that file electronically with the

Our filings with the SEC are available to the public through this website at http://www.sec.gov .

We maintain a corporate website at www.anchiano.com.

Our reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act, including our Annual Reports on Form 10-K,

Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, and amendments to those reports, are accessible through our website,

free of charge, as soon as reasonably practicable after these reports are filed electronically with, or otherwise furnished to,

Information contained on, or that can be accessed through, our website is not incorporated by reference into this Annual

Report on Form 10-K, and you should not consider information on our website to be part of this Annual Report on Form 10-K.

Our reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act, including our Annual Reports

on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, and amendments to those reports,

are accessible through our website, free of charge, as soon as reasonably practicable after these reports are filed electronically

with, or otherwise furnished to, the SEC.

Information contained on, or that can be accessed through, our website is not incorporated

by reference into this Annual Report on Form 10-K, and you should not consider information on our website to be part of this

Annual Report on Form 10-K.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business