What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2025-03-31 compared with 2024-04-01 · 294 added, 249 removed, 184 unchanged (75% of the section changed)

1 unchanged sentence

“ we ,” “ our ” or the “ Company ”) is a clinical stage biotechnology company whose

proprietary INTASYL™ self-delivering RNAi technology platform is designed to make immune cells more effective in killing tumor cells.

proprietary INTASYL® small interfering RNA gene silencing technology is designed to make immune cells more effective in killing tumor

We are developing therapeutics that are designed to leverage INTASYL to precisely target specific proteins that reduce the body’s

2 unchanged sentences

innovative cancer treatments for patients by creating new pathways toward a cancer-free future.

In 2023, the Company implemented a cost rationalization

program driven by its transition from discovery research to product development.

This resulted in a decision not to renew the lease for

office and laboratory space in Marlborough, Massachusetts, which will expire on March 31, 2024.

Beginning in April of 2024, we expect

to continue operations as a remote business with a small laboratory facility in Worcester, Massachusetts for 321 square feet of space

that commenced on March 1, 2024.

Additionally, we rationalized discovery research personnel resulting in headcount reduction by approximately

Expense reductions have been redirected to funding the Phase 1b clinical trial with PH-762 directed toward skin cancer.

INTASYL Platform

The Company operates with a single operating

segment and a single reporting segment – the Clinical segment.

PH-762 is an INTASYL compound designed

to reduce the expression of cell death protein 1 (“PD-1”).

PH-762 is currently being evaluated in a U.S.

multi-center Phase

1b dose-escalating clinical trial through the intratumoral injection of PH-762 for the treatment of patients with cutaneous squamous cell

carcinoma, melanoma and Merkel cell carcinoma.

The trial (NCT 06014086) is designed to evaluate the safety and tolerability of neoadjuvant

use of intratumorally injected PH-762, assess the tumor response, and determine the dose or dose range for continued study of PH-762 and

is expected to enroll up to 30 patients.

In May and December 2024, respectively, a Safety Monitoring Committee (SMC) reviewed data from

the first and second dose cohorts treated with PH-762, and in both instances recommended escalation to the next dose concentration.

total of 7 patients with cutaneous carcinomas have been enrolled in dose cohorts 1 and 2.

The second cohort enrolled a total of 4 patients

who were diagnosed with cutaneous squamous cell carcinoma.

At Day 36 (tumor excision), while patients in the first cohort had stable disease,

a complete response (100% tumor clearance) was reported for 2 patients with cutaneous squamous cell carcinoma.

Partial response (90% tumor

clearance) was reported for 1 patient with cutaneous squamous cell carcinoma and 1 patient had stable disease, having not progressed.

In this trial to date, intratumoral injection of PH-762 has been well tolerated in all enrolled patients and there were no dose-limiting

toxicities or clinically relevant treatment-emergent adverse effects in the patients receiving intratumoral PH-762.

The third dose cohort

is fully enrolled and patients in this cohort are currently in the treatment or follow-up phase of the study.

We expect to complete enrollment

of all patients in the study in the third quarter of 2025.

INTASYL Technology

Overall, RNA is involved in the synthesis, regulation

8 unchanged sentences

Our development efforts are based on our proprietary

INTASYL self-delivering RNAi technology platform.

It is a patented platform from which specific patented compounds are developed.

compounds are comprised of a unique sequence of chemically modified nucleotides (modified small interfering RNA, or siRNAs) that target

a broad range of cell types and tissues.

INTASYL small interfering RNA technology.

It is a patented technology from which specific patented compounds are developed.

INTASYL compounds

are comprised of a unique sequence of chemically modified nucleotides (modified small interfering RNA, or siRNAs) that target a broad

range of cell types and tissues.

The compounds are designed to effectively silence genes that tumors use to evade the immune system.

8 unchanged sentences

spontaneous, cellular uptake with potent, long-lasting intracellular activity.

believe that our INTASYL platform provides the following benefits including, but not limited to:

that our INTASYL technology provides the following benefits including, but not limited to:

Ability to target a broad range of cell types and tissues;

5 unchanged sentences

Readily manufactured under current good manufacturing practices.

INTASYL compounds are

designed to precisely target specific proteins that reduce the body’s ability to fight cancer, without the need for specialized

formulations or drug delivery systems, and are designed to make immune cells more effective in killing tumor cells.

Our efforts are focused

on developing immuno-oncology therapeutics using our INTASYL platform.

We have demonstrated preclinical activity against multiple gene

targets including PD-1, BRD4, CTLA-4, TIGIT and CTGF and have demonstrated preclinical efficacy in both direct-to-tumor injection and

adoptive cell therapy (“ ACT ”) applications with our INTASYL compounds.

The following table summarizes

our product pipeline.

INTASYL compounds are designed

to precisely target specific proteins that reduce the body’s ability to fight cancer, without the need for specialized formulations

or drug delivery systems, and are designed to make immune cells more effective in killing tumor cells.

Our efforts are focused on developing

immuno-oncology therapeutics using our INTASYL technology.

We have demonstrated preclinical activity against multiple gene targets including

PD-1, BRD4, CTLA-4, TIGIT and CTGF and have demonstrated preclinical efficacy in both direct-to-tumor injection and adoptive cell therapy

(“ ACT ”) applications with our INTASYL compounds.

The following table

summarizes our product pipeline.

Below we provide important information and context regarding each compound.

PH-762 is an INTASYL compound designed to reduce

the expression of cell death protein 1 (“ PD-1 ”).

PD-1 is a protein that inhibits T cells’ ability to kill cancer

cells and is a clinically validated target in immunotherapy.

Decreasing the expression of PD-1 can thereby increase the capacity of T

cells, which protect the body from cancer cells and infections, to kill cancer cells.

Our preclinical studies have demonstrated that

direct-to-tumor application of PH-762 resulted in potent anti-tumoral effects and have shown that direct-to-tumor treatment with PH-762

inhibits tumor growth in a dose dependent fashion in PD-1 responsive and refractory models.

PH-762 is an INTASYL compound designed to reduce the

expression of PD-1.

PD-1 is a protein that inhibits T cells’ ability to kill cancer cells and is a clinically validated target in

immunotherapy.

Decreasing the expression of PD-1 can thereby increase the capacity of T cells, which protect the body from cancer cells

and infections, to kill cancer cells.

Our preclinical studies have demonstrated

that direct-to-tumor application of PH-762 resulted in potent anti-tumoral effects and have shown that direct-to-tumor treatment with

PH-762 inhibits tumor growth in a dose dependent fashion in PD-1 responsive and refractory models.

Importantly, direct-to-tumor administration

2 unchanged sentences

support the potential for PH-762 to provide a strong local immune response without the dose immune-related adverse effects seen with systemic

antibody therapy.

PH-762 is currently being evaluated in a U.S.

Phase 1b dose-escalating clinical trial through the intratumoral injection of PH-762 for the treatment of patients with cutaneous squamous

cell carcinoma, melanoma and Merkel cell carcinoma.

The trial is designed to evaluate the safety and tolerability of neoadjuvant use of

intratumorally injected PH-762, assess the tumor response, and determine the dose or dose range for continued study of PH-762 and is expected

to enroll up to 30 patients.

In November 2023, we announced the dosing of the first patient and the trial is currently open for the continued

enrollment of patients.

Given our intention to focus our efforts and resources

clinical trial with PH-762, we have completed the winding down process for our first-in-human clinical trial for PH-762 in

France, which was limited to the treatment of patients with metastatic melanoma.

Safety data from the initial cohort of three patients

in the French clinical trial were evaluated by a data monitoring committee in the first quarter of 2023.

The safety data review disclosed

no dose-limiting toxicity, and no drug-related severe or serious adverse events.

Due to INTASYL’s

ease of administration, we have shown that our compounds can easily be incorporated into current ACT manufacturing processes.

T cells are usually taken from a patient's own blood or tumor tissue, grown in large numbers in a laboratory, and then given back to the

patient to help the immune system fight cancer.

By treating T cells with our INTASYL compounds while they are being grown in the laboratory,

we believe our INTASYL compounds can improve these immune cells to make them more effective in killing cancer.

antibody therapy.PH-762 is currently being evaluated in a U.S.

multi-center Phase 1b dose-escalating clinical trial through the intratumoral

injection of PH-762 for the treatment of patients with cutaneous squamous cell carcinoma, melanoma and Merkel cell carcinoma.

(NCT 06014086) is designed to evaluate the safety and tolerability of neoadjuvant use of intratumorally injected PH-762, assess the tumor

response, and determine the dose or dose range for continued study of PH-762 and is expected to enroll up to 30 patients.

2023, we announced the dosing of the first patient under a previously cleared Investigational New Drug (“ IND ”) application

Food and Drug Administration, and the trial is currently open for the continued enrollment of patients.

In May and December

2024, respectively, a Safety Monitoring Committee (SMC) reviewed data from the first and second dose cohorts treated with PH-762, and

in both instances recommended escalation to the next dose concentration.

A total of 7 patients with cutaneous carcinomas have been enrolled

in dose cohorts 1 and 2.

The second cohort enrolled a total of 4 patients who were diagnosed with cutaneous squamous cell carcinoma.

Day 36 (tumor excision), while patients in the first cohort had stable disease, a complete response (100% tumor clearance) was reported

for 2 patients with cutaneous squamous cell carcinoma.

Partial response (90% tumor clearance) was reported for 1 patient with cutaneous

squamous cell carcinoma and 1 patient had stable disease, having not progressed.

Intratumoral injection of PH-762 has

been well tolerated in all patients enrolled in the trial to date.

There were no dose-limiting toxicities or clinically relevant treatment-emergent

adverse effects in the patients receiving intratumoral PH-762.

The third dose cohort is fully enrolled and patients in this cohort are

currently in the treatment or follow-up phase of the study.

We expect to complete enrollment of all patients in the study in the third

quarter of 2025.

Due to INTASYL’s ease of administration, we have shown that our compounds can easily be incorporated into current

ACT manufacturing processes.

In ACT, immune cells such as T cells, natural killer cells or dendritic cells are taken from a patient’s

or donor’s blood or tumor tissue, grown in large numbers in a laboratory, and then given back to the patient to help the immune

system fight cancer.

By treating a patient’s T cells with our INTASYL compounds while they are being grown outside the body, we

believe our INTASYL compounds can improve these immune cells to make them more effective in killing cancer.

Preclinical data generated

3 unchanged sentences

infiltrating lymphocytes (“ DP TIL ”) with PH-762 increased their tumor killing activity by two-fold.

In February 2021, we entered into a clinical co-development

collaboration agreement (the “ Clinical Co-Development Agreement ”) with AgonOx to develop a T cell-based therapy using

PH-762 and AgonOx’s DP TIL.

Under the Clinical Co-Development Agreement, we agreed to reimburse AgonOx up to $4 million in expenses

incurred to conduct a Phase 1 clinical trial of PH-762 treated DP TIL in patients with advanced melanoma and other advanced solid tumors.

As of December 31, 2023, there was approximately $2.8 million of remaining costs not yet incurred under the Clinical Co-Development Agreement.

We are also eligible to receive certain future development milestones and low single-digit sales-based royalty payments from AgonOx’s

licensing of its DP TIL technology.

PH-762 treated DP TIL are being evaluated in a

Phase 1 clinical trial in the U.S.

with up to 18 patients with advanced melanoma and other advanced solid tumors by AgonOx.

trial objectives are to evaluate the safety and to study the potential for enhanced therapeutic benefit from the administration of PH-762

treated DP TIL.

We announced the first patient was dosed in August 2023 and the trial is open for the continued enrollment of patients.

PH-894 is an INTASYL compound that is designed

to silence BRD4, a protein that controls gene expression in both T cells and tumor cells, thereby effecting the immune system as well

as the tumor.

Intracellular and/or commonly considered “undruggable” targets, such as BRD4, represent a challenge for small

molecule and antibody therapies.

In February 2021, we entered into a

clinical co-development collaboration agreement (the “ Clinical Co-Development Agreement ”) with AgonOx to develop a

T cell-based therapy using PH-762 and AgonOx’s DP TIL.

Under the Clinical Co- Development Agreement, we had agreed to reimburse

AgonOx up to $4 million in expenses incurred to conduct a Phase 1 clinical trial of PH-762 treated DP TIL in patients with advanced melanoma

and other advanced solid tumors.

In May 2024, we terminated the Clinical

Co-Development Agreement with AgonOx, which such termination was effective immediately.

Effective as of the date of termination, the Clinical

Co-Development Agreement and our continuing obligations and those of AgonOx thereunder were terminated in their entirety.

We are no longer

required to provide financial support for the development of costs incurred under the Clinical Co-Development Agreement and we are no

longer entitled to future development milestones or royalty payments from AgonOx’s licensing of its DP TIL technology.

to pay to AgonOx all monetary obligations that accrued prior to the termination of the Clinical Co-Development Agreement.

Remaining payments

to be made to AgonOx as of December 31, 2024 totaled $34,320, which primarily relate to accrued obligations for patient fees and other

miscellaneous costs as of the date of termination.

Pursuant to the terms of the Clinical Co-Development Agreement, each of the Company

and AgonOx shall be responsible for its own costs and expenses incurred in connection with the wind-down of the Phase 1 clinical trial.

Prior to the termination of the Clinical

Co-Development Agreement with AgonOx, PH-762 treated DP TIL were being evaluated in a Phase 1 clinical trial in the U.S.

with up to 18

patients with advanced melanoma and other advanced solid tumors by AgonOx.

The primary trial objectives were to evaluate the safety and

to study the potential for enhanced therapeutic benefit from the administration of PH-762 treated DP TIL.

AgonOx had enrolled three patients.

The first two patients were treated with DP TIL only and a third patient was treated with a combination of DP TIL and PH-762.

results for the single patient who received a combination of DP TIL and PH-762 showed tumor size reductions of 65%, 100% and 81%, respectively,

in three melanoma lesions.

PH-894 is an INTASYL compound that is designed to silence

BRD4, a protein that controls gene expression in both T cells and tumor cells, thereby affecting the immune system as well as the tumor.

Intracellular and/or commonly considered “undruggable” targets, such as BRD4, represent a challenge for small molecule and

antibody therapies.

Therefore, what sets this compound apart is its dual mechanism:

PH-894 suppression of BRD4 in T cells

results in T cell activation, and suppression of BRD4 in tumor cells results in tumors becoming more sensitive to being killed by T cells.

Preclinical studies conducted have demonstrated

that PH-894 resulted in a strong, concentration dependent and durable silencing of BRD4 in T cells and in various cancer cells.

to PH-762, preclinical studies have also shown that direct-to-tumor application of PH-894 resulted in potent and statistically significant

PH-894 suppression of BRD4 in T cells results in T

cell activation, and suppression of BRD4 in tumor cells results in tumors becoming more sensitive to being killed by T cells.

Preclinical studies conducted have demonstrated that

PH-894 resulted in a strong, concentration dependent and durable silencing of BRD4 in T cells and in various cancer cells.

PH-762, preclinical studies have also shown that direct-to-tumor application of PH-894 resulted in potent and statistically significant

anti-tumoral effects against distant untreated tumors, indicative of a systemic anti-tumor response.

2 unchanged sentences

We have completed

the investigational new drug application (“ IND ”)-enabling studies and are in the process of continuing to finalize

the study reports required for an IND submission with PH-894.

As a result of the reprioritization to advance our clinical trial with PH-762

in the U.S., we have elected to defer the IND submission for PH-894.

the IND-enabling studies and are in the process of finalizing the study reports required for an IND submission with PH-894.

of the reprioritization to advance our clinical trial with PH-762 in the U.S., we have elected to defer the IND submission for PH-894.

Synergies With Other Therapies

Preclinical studies with our INTASYL compounds

in combination with antibodies resulted in enhanced potency in vivo.

The combination of INTASYL with antibodies may also increase the

number of addressable drug targets.

Unlike other antibody combination approaches, INTASYL can target multiple protein drug targets in

a specific therapeutic dose, thereby enhancing potency while maintain a favorable tolerability and safety profile.

We have demonstrated preclinical efficacy with

INTASYL in ACT applications.

In preclinical studies, INTASYL was shown to enhance the activity of ACT therapies, including with tumor

infiltrating lymphocytes and natural killer cells.

As demonstrated in these preclinical studies, INTASYL is easily incorporated into current

ACT manufacturing processes.

Preclinical studies with our INTASYL compounds in combination

with antibodies resulted in enhanced potency in vivo.

The combination of INTASYL with antibodies may also increase the number of addressable

drug targets.

Unlike other antibody combination approaches, INTASYL can target multiple protein drug targets in a specific therapeutic

dose, thereby enhancing potency while maintaining a favorable tolerability and safety profile.

We have demonstrated preclinical efficacy with INTASYL

in ACT applications.

In preclinical studies, INTASYL was shown to enhance the activity of ACT therapies, including with tumor infiltrating

lymphocytes and natural killer cells.

As demonstrated in these preclinical studies, INTASYL is easily incorporated into current ACT manufacturing

Intellectual Property

9 unchanged sentences

discovery platform.

We have also obtained rights to various patents

and patent applications under licenses with third parties, which require us to pay royalties, milestone payments, or both.

of patent protection for biotechnology products and processes, including ours, remains uncertain, both in the U.S.

and in other important

markets, because the scope of protection depends on decisions of patent offices, courts and lawmakers in these countries.

certainty that our existing patents or others, if obtained, will afford us substantial protection or commercial benefit.

Similarly, there

is no assurance that our pending patent applications or patent applications licensed from third parties will ultimately be granted as

patents or that those patents that have been issued or are issued in the future will stand if they are challenged in court.

our license agreements on an ongoing basis and may from time to time terminate licenses to technology that we do not intend to employ

in our technology platforms, or in our product discovery or development activities.

We have also obtained rights to various patents and

patent applications under licenses with third parties, which require us to pay royalties, milestone payments, or both.

The degree of patent protection for biotechnology products

and processes, including ours, remains uncertain, both in the U.S.

and in other important markets, because the scope of protection depends

on decisions of patent offices, courts and lawmakers in these countries.

There is no certainty that our existing patents or others, if

obtained, will afford us substantial protection or commercial benefit.

Similarly, there is no assurance that our pending patent applications

or patent applications licensed from third parties will ultimately be granted as patents or that those patents that have been issued or

are issued in the future will stand if they are challenged in court.

We assess our license agreements on an ongoing basis and may from

time to time terminate licenses to technology that we do not intend to employ in our technology platforms, or in our product discovery

or development activities.

Patents and Patent Applications

5 unchanged sentences

Other Markets

Our portfolio includes 81 issued patents, 73 of

which cover our INTASYL platform.

Our portfolio includes 77 issued patents, 69 of which

cover our INTASYL technology.

There are 19 patent families broadly covering both the composition and methods of use of our self-delivering

INTASYL platform technology and uses of our INTASYL compounds targeting immune checkpoint, cellular differentiation and metabolism targets

for ex vivo cell-based cancer immunotherapies.

The INTASYL platform patents are scheduled to expire between 2029 and 2038.

Furthermore, there are 40 patent applications,

encompassing what we believe to be important new RNAi compounds and their use as therapeutics, chemical modifications of RNAi compounds

that improve the compounds’ suitability for therapeutic uses (including delivery) and compounds directed to specific targets ( i.e.

that address specific disease states).

INTASYL platform technology and uses of our INTASYL compounds targeting immune checkpoints for cancer therapy, as well as cellular differentiation

and metabolism targets for Adoptive Cell Therapy cancer immunotherapies.

The INTASYL technology patents are scheduled to expire between

2029 and 2038.

Furthermore, there are 26 patent applications, encompassing

what we believe to be important new RNAi compounds and their use as therapeutics, chemical modifications of RNAi compounds that improve

the compounds’ suitability for therapeutic uses (including delivery) and compounds directed to specific targets ( i.e.

address specific disease states).

The patents that may issue from these pending patent applications will, if issued, be set to expire

3 unchanged sentences

Key Intellectual Property License Agreements

As we develop our own proprietary compounds, we

continue to evaluate our in-licensed portfolio as well as the field for new technologies that could be in-licensed to further enhance

our intellectual property portfolio and unique intellectual property position.

In September 2011, the Company entered into an

agreement with Advanced RNA Technologies, LLC (“ Advirna ”), pursuant to which Advirna assigned to us its existing patent

and technology rights related to the INTASYL technology in exchange for an annual maintenance fee, a one-time milestone payment upon the

future issuance of the first patent with valid claims covering the assigned patent and technology rights and the issuance of shares of

common stock of the Company equal to 5% of the Company’s fully-diluted shares outstanding at the time of issuance.

In 2012, we issued

shares of common stock of the Company to Advirna equal to 5% of our fully-diluted shares outstanding at the time of issuance and paid

$350,000 to Advirna upon the issuance of the first patent in 2014.

Additionally, we also pay to Advirna an annual maintenance fee of $100,000

and are required to pay low single-digit royalties on any licensing revenue received by us with respect to future licensing of the assigned

Advirna patent and technology rights.

To date, any royalties owed to Advirna under the Advirna agreement have been minimal.

As we develop our own proprietary compounds, we continue

to evaluate our in-licensed portfolio as well as the field for new technologies that could be in-licensed to further enhance our intellectual

property portfolio and unique intellectual property position.

In September 2011, the Company entered into an agreement

with Advanced RNA Technologies, LLC (“ Advirna ”), pursuant to which Advirna assigned to us its existing patent and technology

rights related to the INTASYL technology in exchange for an annual maintenance fee, a one-time milestone payment upon the future issuance

of the first patent with valid claims covering the assigned patent and technology rights and the issuance of shares of Common Stock equal

to 5% of the Company’s fully-diluted shares outstanding at the time of issuance.

In 2012, we issued shares of Common Stock to Advirna

equal to 5% of our fully-diluted shares outstanding at the time of issuance and paid $350,000 to Advirna upon the issuance of the first

patent in 2014.

Additionally, we also pay to Advirna an annual maintenance fee of $100,000 and are required to pay low single-digit royalties

on any licensing revenue received by us with respect to future licensing of the assigned Advirna patent and technology rights.

any royalties owed to Advirna under the Advirna agreement have been minimal.

Our rights under the Advirna agreement will expire

1 unchanged sentence

(i) the expiration of the last-to-expire of the “patent rights” (as defined therein) included in the

Advirna agreement or (ii) the abandonment of the last-to-be abandoned of such patents, unless earlier terminated in accordance with

Advirna agreement and (ii) the abandonment of the last-to-be abandoned of such patents, unless earlier terminated in accordance with

the provisions of the Advirna agreement.

1 unchanged sentence

rights for fields of use outside human therapeutics.

Manufacturing and

do not have any manufacturing capability and therefore we currently rely on and intend to continue to rely on contract manufacturing organizations

Manufacturing and Supply

not have any manufacturing capability and therefore we currently rely on and intend to continue to rely on contract manufacturing organizations

to produce our product candidates in accordance with regulatory requirements.

3 unchanged sentences

We expect that we will continue to rely on and contract with third parties to manufacture our product candidates in the

The biotechnology and pharmaceutical industries,

including the immuno-oncology field, are a constantly evolving landscape with rapidly advancing technologies and significant competition.

There are a number of competitors in the immuno-oncology field including large and small pharmaceutical and biotechnology companies, academic

The biotechnology and pharmaceutical industries, including

the immuno-oncology field, are a constantly evolving landscape with rapidly advancing technologies and significant competition.

are a number of competitors in the immuno-oncology field including large and small pharmaceutical and biotechnology companies, academic

institutions, government agencies and other private and public research organizations.

3 unchanged sentences

Review and Approval of Drugs in the United States

The United States and many other countries

extensively regulate the preclinical and clinical testing, manufacturing, labeling, storage, record-keeping, advertising, promotion, export,

marketing and distribution of drugs and biologic products.

Food and Drug Administration (“ FDA ”) regulates

pharmaceutical and biologic products under the FFDCA, the Public Health Service Act and other federal statutes and regulations.

The United States and many other countries extensively

regulate the preclinical and clinical testing, manufacturing, labeling, storage, record-keeping, advertising, promotion, export, marketing

and distribution of drugs and biologic products.

Food and Drug Administration (“ FDA ”) regulates pharmaceutical

and biologic products under the FFDCA, the Public Health Service Act and other federal statutes and regulations.

To obtain approval of our future product candidates

9 unchanged sentences

initial marketing of our products.

The first stage of the FDA approval process for

a new biologic or drug involves completion of preclinical studies and the submission of the results of these studies to the FDA.

data, together with proposed clinical protocols, manufacturing information, analytical data and other information submitted to the FDA

through an IND, must become effective before human clinical trials may commence.

Preclinical studies generally involve evaluation of product

characteristics and animal studies to assess the efficacy and safety of the product candidate.

Many of these studies must be conducted

in accordance with the FDA’s current Good Laboratory Practices, the Animal Welfare Act, and other applicable regulations.

After the IND becomes effective, a company may

commence human clinical trials.

The first stage of the FDA approval process for a new

biologic or drug involves completion of preclinical studies and the submission of the results of these studies to the FDA.

together with proposed clinical protocols, manufacturing information, analytical data and other information submitted to the FDA through

an IND, must become effective before human clinical trials may commence.

Preclinical studies generally involve evaluation of product characteristics

and animal studies to assess the efficacy and safety of the product candidate.

Many of these studies must be conducted in accordance with

the FDA’s current Good Laboratory Practices, the Animal Welfare Act, and other applicable regulations.

After the IND becomes effective, a company may commence

human clinical trials.

These are typically conducted in three sequential phases, but the phases may overlap.

Phase 1 trials consist

of testing the product candidate in a small number of patients or healthy volunteers, primarily for safety at one or more doses.

Phase 1 trials consist of

testing the product candidate in a small number of patients or healthy volunteers, primarily for safety at one or more doses.

trials, in addition to safety, evaluate the efficacy of the product candidate in a patient population somewhat larger than Phase 1 trials.

2 unchanged sentences

at the institutions participating in the trials, prior to commencement of each clinical trial.

To obtain FDA marketing authorization, a company

must submit to the FDA the results of the preclinical and clinical testing, together with, among other things, detailed information on

the manufacture and composition of the product candidate, in the form of a new drug application (“ NDA ”), or, in the

case of a biologic, a biologics license application (“ BLA ”).

The amount of time taken by the FDA to approve

a NDA or BLA will depend upon a number of factors, including whether the product candidate has received priority review, the quality of

the submission and studies presented, the potential contribution that the compound will make in improving the treatment of the disease

in question and agency resources.

The FDA maintains several programs to facilitate

and expedite the development and review of applications that are intended for the treatment of a serious or life-threatening disease or

condition that meet certain other criteria, including Fast Track Designation, Breakthrough Designation, Priority Review, and the Accelerated

Approval pathway.

To obtain FDA marketing authorization, a company must

submit to the FDA the results of the preclinical and clinical testing, together with, among other things, detailed information on the

manufacture and composition of the product candidate, in the form of a new drug application (“ NDA ”), or, in the case

of a biologic, a biologics license application (“ BLA ”).

The amount of time taken by the FDA to approve an NDA

or BLA will depend upon a number of factors, including whether the product candidate has received priority review, the quality of the

submission and studies presented, the potential contribution that the compound will make in improving the treatment of the disease in

question and agency resources.

The FDA maintains several programs to facilitate and

expedite the development and review of applications that are intended for the treatment of a serious or life-threatening disease or condition

that meet certain other criteria, including Fast Track Designation, Breakthrough Designation, Priority Review, and the Accelerated Approval

We anticipate that our products will be manufactured

7 unchanged sentences

Act, the Toxic Substance Control Act and the Resource Conservation and Recovery Act and other applicable environmental statutes.

approval, the FDA and certain state agencies periodically inspects drug and biologic manufacturing facilities to ensure continued compliance

approval, the FDA and certain state agencies periodically inspect drug and biologic manufacturing facilities to ensure continued compliance

with the cGMP.

6 unchanged sentences

if problems concerning safety or efficacy of the product occur following approval.

The labeling, advertising, promotion, marketing

and distribution of a drug or biologic product also must be in compliance with FDA and Federal Trade Commission requirements which include,

The labeling, advertising, promotion, marketing and

distribution of a drug or biologic product also must be in compliance with FDA and Federal Trade Commission requirements which include,

among others, standards and regulations for off-label promotion, industry sponsored scientific and educational activities, promotional

18 unchanged sentences

longer or shorter than that required for FDA approval.

In the European Union, Canada and Australia, regulatory requirements and approval

processes are similar, in principle, to those in the U.S.

European Union Data Laws For Review and Approval of Drugs in the

European Union Including France

The collection and use of personal health data

and other personal information in the European Union (“ EU ”) is governed by the provisions of the General Data Protection

In the European Union, the United Kingdom, Canada and Australia, regulatory requirements

and approval processes are similar, in principle, to those in the U.S.

European Union Data Laws for Review and Approval of Drugs in the European

Union Including France

The collection and use of personal health data and

other personal information in the European Union (“ EU ”) is governed by the provisions of the General Data Protection

Regulation (“ GDPR ”), which came into force in May 2018, and related implementing laws in individual EU Member States.

In addition, following the United Kingdom’s (“ UK ”) formal departure from the EU on January 31, 2020 and the end

of the transition period on December 31, 2020, the UK has become a “third country” for the purposes of EU data protection

In addition, following the United Kingdom’s (“ UK ”) formal departure from the EU on January 31, 2020, and the

end of the transition period on December 31, 2020, the UK has become a “third country” for the purposes of EU data protection

A “third country” is a country other than the EU Member States and the three additional European Economic Area countries

11 unchanged sentences

The GDPR increased responsibility and liability in relation to personal data that we process.

The GDPR imposes a number of strict obligations

and restrictions on the ability to process (processing includes collection, analysis and transfer of) personal data, including health

data from clinical trials and adverse event reporting.

The GDPR also includes requirements relating to the consent of the individuals

to whom the personal data relates, the information provided to the individuals prior to processing their personal data or personal health

data, notification of data processing obligations to the national data protection authorities and the security and confidentiality of

the personal data.

The GDPR also prohibits the transfer of personal data to countries outside of the EU that are not considered by the

EU to provide an adequate level of data protection, except if the data controller meets very specific requirements.

These countries include

the United States, and following the end of the six month period as laid out in the TCA, it may include the UK if no adequacy decision

is given prior to this.

Following the Schrems II decision of the Court of Justice of the European Union on July 16, 2020, there is uncertainty

as to the general permissibility of international data transfers under the GDPR.

In light of the implications of this decision we may

face difficulties regarding the transfer of personal data from the EU to third countries.

The European Data Protection Board has adopted

draft recommendations for data controllers and processors who export personal data to third countries regarding supplementary measures

to ensure compliance with the GDPR when transferring personal data outside of the EU.

These recommendations were submitted to public consultation

until December 21, 2020, however it is unclear when and in which form these recommendations will be published in final form.

Failure to comply with the requirements of the

GDPR and the related national data protection laws of the EU Member States may result in significant monetary fines, other administrative

penalties and a number of criminal offenses (punishable by uncapped fines) for organizations and in certain cases their directors and

officers as well as civil liability claims from individuals whose personal data was processed.

Data protection authorities from the different

EU Member States may still implement certain variations, enforce the GDPR and national data protection laws differently, and introduce

additional national regulations and guidelines, which adds to the complexity of processing personal data in the EU.

Guidance developed

at both EU level and at the national level in individual EU Member States concerning implementation and compliance practices are often

updated or otherwise revised.

The GDPR imposes a number of strict obligations and

restrictions on the ability to process (processing includes collection, analysis and transfer of) personal data, including health data

from clinical trials and adverse event reporting.

The GDPR also includes requirements relating to the consent of the individuals to whom

the personal data relates, the information provided to the individuals prior to processing their personal data or personal health data,

notification of data processing obligations to the national data protection authorities and the security and confidentiality of the personal

The GDPR also prohibits the transfer of personal data to countries outside of the EU that are not considered by the EU to provide

an adequate level of data protection, except if the data controller meets very specific requirements.

These countries include the United

States, and following the end of the six month period as laid out in the TCA, it may include the UK if no adequacy decision is given prior

Following the Schrems II decision of the Court of Justice of the European Union on July 16, 2020, there is uncertainty as to

the general permissibility of international data transfers under the GDPR.

In light of the implications of this decision we may face difficulties

regarding the transfer of personal data from the EU to third countries.

The European Data Protection Board has adopted draft recommendations

for data controllers and processors who export personal data to third countries regarding supplementary measures to ensure compliance

with the GDPR when transferring personal data outside of the EU.

These recommendations were submitted to public consultation until December

21, 2020, however it is unclear when and in which form these recommendations will be published in final form.

Failure to comply with the requirements of the GDPR

and the related national data protection laws of the EU Member States may result in significant monetary fines, other administrative penalties

and a number of criminal offenses (punishable by uncapped fines) for organizations and in certain cases their directors and officers as

well as civil liability claims from individuals whose personal data was processed.

Data protection authorities from the different EU Member

States may still implement certain variations, enforce the GDPR and national data protection laws differently, and introduce additional

national regulations and guidelines, which adds to the complexity of processing personal data in the EU.

Guidance developed at both EU

level and at the national level in individual EU Member States concerning implementation and compliance practices are often updated or

otherwise revised.

There is, moreover, a growing trend towards required

5 unchanged sentences

penalties against us, harm to our reputation, and adversely impact our business and operating results.

The uncertainty regarding the

interplay between different regulatory frameworks, such as the Clinical Trials Regulation and the General Data Protection Regulation,

further adds to the complexity that we face with regard to data protection regulation.

The uncertainty regarding the interplay

between different regulatory frameworks, such as the Clinical Trials Regulation and the General Data Protection Regulation, further adds

to the complexity that we face with regard to data protection regulation.

Environmental Compliance

Our research and development activities involve

the controlled use of potentially harmful biological materials as well as hazardous materials, chemicals and various radioactive compounds.

Our research and development activities involve the

controlled use of potentially harmful biological materials as well as hazardous materials, chemicals and various radioactive compounds.

We are subject to federal, state and local laws and regulations governing the use, storage, handling and disposal of these materials and

8 unchanged sentences

Human Capital Management

As of December 31, 2023, we had eight full-time

employees and one part-time employee at our facility in Marlborough, Massachusetts.

None of our employees are represented by a labor union

or covered by a collective bargaining agreement, nor have we experienced any work stoppages.

We continually evaluate our business needs and

weigh the use of in-house expertise and capacity with outsourced expertise and capacity.

We currently outsource substantially all preclinical

and clinical trial work to third party contract research organizations and drug manufacturing contractors.

Our ability to identify,

attract, retain and integrate additional qualified key personnel is also critical to our success and the competition for skilled research,

product development, regulatory and technical personnel is intense.

To attract qualified applicants, we offer a total rewards package

consisting of base salary and cash target bonus, a comprehensive benefit package and equity compensation for every employee.

Bonus opportunity

and equity compensation increase as a percentage of total compensation based on level of responsibility.

Actual bonus payouts are

based on performance.

As of December 31, 2024, we had five full-time employees.

One employee utilizes a rented lab space, and the other four employees are primarily remote.

None of our employees are represented by

a labor union or covered by a collective bargaining agreement, nor have we experienced any work stoppages.

We continually evaluate our business needs and weigh

the use of in-house expertise and capacity with outsourced expertise and capacity.

We currently outsource the functions of our accounting

and finance department to a third-party consulting organization.

We currently outsource substantially all preclinical and clinical trial

work to third party contract research organizations and drug manufacturing contractors.

Our ability to identify, attract,

retain and integrate additional qualified key personnel is also critical to our success and the competition for skilled research, product

development, regulatory and technical personnel is intense.

To attract qualified applicants, we offer a total rewards package consisting

of base salary and cash target bonus, a comprehensive benefit package and equity compensation.

Bonus opportunity and equity compensation

increase as a percentage of total compensation based on level of responsibility.

Actual bonus payouts are based on performance.

A majority of Phio’s

employees have obtained advanced degrees in their professions and we support our employees’ further development with individualized

development plans, mentoring, coaching, group training, conference attendance and financial support including tuition reimbursement.

development plans, mentoring, coaching, group training, and conference attendance.

Corporate Information

Effective January 26, 2023, the Company completed

a 1-for-12 reverse stock split of the Company’s outstanding common stock.

The reverse stock split did not reduce the number of

authorized shares of the Company’s common or preferred stock.

All share and per share amounts have been adjusted to give effect

to the reverse stock split.

We were incorporated in the state of Delaware in

2011 as RXi Pharmaceuticals Corporation.

On November 19, 2018, we changed our name to Phio Pharmaceuticals Corp., to reflect our transition

from a platform company to one that is fully committed to developing groundbreaking immuno-oncology therapeutics.

Our executive offices

are located at 257 Simarano Drive, Suite 101, Marlborough, MA 01752, and our telephone number is (508) 767-3861.

Effective July 5, 2024, the Company

completed a 1-for-9 reverse stock split of the Company’s outstanding Common Stock, including reclassifying an amount equal to the

reduction in par value to additional paid-in capital.

The reverse stock split did not reduce the number of authorized shares of the Company’s

common or preferred stock.

All share and per share amounts have been adjusted to give effect to the reverse stock split.

We were incorporated in the state of Delaware in 2011 as RXi Pharmaceuticals Corporation.

November 19, 2018, we changed our name to Phio Pharmaceuticals Corp., to reflect our transition from a platform company to one that is

fully committed to developing groundbreaking immuno-oncology therapeutics.

In 2023, we implemented a cost rationalization program

driven by our transition from discovery research to product development.

This resulted in a decision not to renew the lease for office

and laboratory space in Marlborough, Massachusetts, which expired on March 31, 2024.

Beginning in April 2024, we have continued operations

as a remote business with a laboratory facility in Worcester, Massachusetts.

Our executive offices are located at 11 Apex Drive, Suite

300A PMB 2006, Marlborough, Massachusetts 01752 and our telephone number is (508) 767-3861.

The Company’s website address is http://www.phiopharma.com .

5 unchanged sentences

on our website the charters of our audit, compensation, nominating and governance committees, as well as our corporate code of ethics

The SEC maintains an internet site that contains

reports, proxy and information statements, and other information regarding Phio and other issuers that file electronically with the SEC.

The SEC’s website address is http://www.sec.gov .

The contents of this website, and our website, are not incorporated by reference

into this report and should not be considered to be part of this report.

The SEC maintains an internet site that contains reports,

proxy and information statements, and other information regarding Phio and other issuers that file electronically with the SEC.

website address is http://www.sec.gov .

The contents of this website, and our website, are not incorporated by reference into this

report and should not be considered to be part of this report.

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