What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2024-03-05 compared with 2023-03-08 · 51 added, 52 removed, 248 unchanged (29% of the section changed)

We are a biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology.

We are a clinical-stage biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology.

We seek to develop drug candidates in the precision medicine space, and our processes for selection and clinical development of drug candidates is based on scientific insights into cancer-promoting factors, as well as on our understanding of the clinical landscape and regulatory requirements.

9 unchanged sentences

PRODUCTS UNDER DEVELOPMENT

In May 2021, we licensed exclusive worldwide commercial rights to NXP800, a novel orally bioavailable small molecule that was discovered in a screen for Heat Shock Factor 1 (“HSF1”) pathway inhibitors;

NXP800 was discovered at the Institute for Cancer Research (“ICR”) in London, England.

In May 2021, we licensed exclusive worldwide commercial rights to NXP800, a novel small molecule that exerts its biologic activity through activation of the kinase general control nonderepressible 2 (“GCN2”), and was discovered at the Institute for Cancer Research (“ICR”) in London, England.

Our license agreement with the ICR is subject to certain milestone and royalty payments.

2 unchanged sentences

Scientific Background

NXP800 activates the GCN2 kinase inducing inhibition of cap-dependent protein translation and activation of the integrated stress response leading to cancer cell death.

In preclinical studies, treatment with NXP800 inhibited tumor growth in xenografts of ovarian cancer that harbored a loss of function mutation in the ARID1a gene.

Based on this work, we plan to evaluate the safety and efficacy of NXP800 in ARID1a-mutated ovarian carcinoma, which is a cancer type comprised primarily of two histologies:

ovarian clear cell carcinoma (“OCCC”) and endometrioid ovarian carcinoma (“EOC”), and to investigate the use of ARID1a mutations as a potential patient selection marker for additional types of cancer.

Based on this work, we are currently evaluating the safety and efficacy of NXP800 in ARID1a-mutated ovarian carcinoma, which is a cancer type comprised primarily of two histologies:

ovarian clear cell carcinoma (“OCCC”) and endometrioid ovarian carcinoma (“EOC”), and investigating the use of ARID1a mutations as a potential patient selection marker for additional types of cancer.

In addition, in preclinical studies, treatment with NXP800 inhibited tumor growth in patient-derived xenograft ("PDX") models of cholangiocarcinoma.

The safety and efficacy of NXP800 in this indication is currently being evaluated through an investigator-sponsored study conducted in collaboration with the Mayo Clinic.

The genetic screening for mutations in the ARID1a gene is included in commercially available next generation sequencing kits.

NXP800 Clinical Development Plan

NXP800 Clinical Development

A comprehensive preclinical data package supported the approval of the Clinical Trial Application (“CTA”) by the Medicines and Healthcare Regulatory Agency (“MHRA”) in the United Kingdom, and the Investigational New Drug (“IND”) Application submission by the FDA.

In December 2021, we announced the commencement of the Phase 1 study for NXP800.

In December 2021, we announced the commencement of the Phase 1 study

The Phase 1 study is comprised of two parts:

dose-escalation Phase 1a, and an expansion Phase 1b.

In the ongoing Phase 1a, we have been evaluating the safety and tolerability of NXP800 in patients with advanced solid tumors to identify potential doses and dosing schedules for the Phase 1b.

The Phase 1a is nearing completion and the Phase 1b is expected to begin in the first half of 2023.

In the Phase 1b, the safety and preliminary anti-tumor activity of NXP800 will

be initially evaluated in women with platinum-resistant, ARID1a-mutated OCCC and EOC.

dose-escalation Phase 1a, which was completed in April 2023, and an expansion Phase 1b.

In the Phase 1a, we evaluated the safety, tolerability and pharmacokinetic properties of NXP800 in patients with advanced solid tumors to identify potential doses and dosing schedules for the Phase 1b.

In April 2023, we announced the commencement of the Phase 1b, in which the safety and preliminary anti-tumor activity of NXP800 will be evaluated in women with platinum-resistant, ARID1a-mutated ovarian carcinoma.

In December 2022, we announced that the FDA granted Fast Track Designation status to NXP800 for the treatment of patients with platinum-resistant, ARID1a-mutated ovarian carcinoma.

Moreover, we recently announced that the European Network of Gynecological Oncology Trial Groups and the GOG Foundation, Inc., the world's premier gynecology oncology clinical trials consortia, will lead the Phase 1b clinical trial in ARID1a-mutated ovarian carcinoma.

Additional cohorts/trials in patients with other types of solid tumors may also be explored based on emerging data.

In January 2023, we announced that the European Network of Gynecological Oncology Trial Groups and the GOG Foundation, Inc., the world's premier gynecology oncology clinical trials consortia, will lead the Phase 1b clinical trial in ARID1a-mutated ovarian carcinoma.

In December 2023, we announced a collaboration with Mayo Clinic to conduct an investigator-sponsored clinical trial in patients with cholangiocarcinoma.

In August 2023, we announced that the FDA granted Orphan Drug Designation to NXP800 for the treatment of patients with cholangiocarcinoma.

Addressing an Unmet Need in Clear Cell Ovarian Cancer and Advanced-stage Endometrioid Ovarian Carcinoma

10 unchanged sentences

In this ovarian subset, the progression-free survival at three years for women diagnosed with stage III/IV disease is a dismal 20% for stage III and 0% for stage IV, representing a clear unmet medical need.

OCCC and EOC are subtypes of epithelial ovarian carcinoma whose clinical characteristics are distinct from those of high-grade serous ovarian carcinoma.

OCCC and EOC are subtypes of epithelial ovarian carcinoma, which have clinical characteristics distinct from those of high-grade serous ovarian carcinoma.

They exhibit a unique biological profile that is markedly different from those of other histologic types.

1 unchanged sentence

Market Potential/Addressable Patient Population in Additional Solid Tumor Types

In preclinical trials, NXP800 has also demonstrated anti-tumor activity in in-vivo xenograft models of gastric, and endometrial cancer bearing ARID1a mutation.

This preclinical work suggests the potential for the use of ARID1a mutation as a potential patient selection marker in these additional tumor types, which could potentially support a tumor agnostic development strategy wherein patients are selected for treatment based on the cancer’s genetic and molecular features without regard to the type or location of the cancer.

In preclinical trials, NXP800 has also demonstrated anti-tumor activity in in-vivo xenograft models of gastric, and endometrial cancer bearing ARID1a mutation, and in PDX models of cholangiocarcinoma, which provide several development opportunities for NXP800.

In August 2021, we licensed worldwide commercial rights to NXP900 from the University of Edinburgh in Scotland.

NXP900 is a targeted-therapy, small molecule drug candidate that inhibits the proto-oncogene c-Src ( “SRC”) and YES1 kinases.

We have completed the IND-enabling studies and plan to submit an IND application to the FDA, or an equivalent submission with a foreign agency, in order to begin a Phase 1a dose-escalation study of NXP900 in solid tumors in the first half of 2023.

Subsequently, upon successful completion of the dose-escalation study, we plan to conduct a Phase 1b clinical trial to investigate NXP900 in solid tumors where the SRC and/or YES1 pathways are overactivated and implicated in the disease etiology.

In May 2023, we announced the IND was cleared by the FDA which included a Phase 1 protocol and comprised of two parts:

a dose-escalation Phase 1a and an expansion Phase 1b.

In September 2023, we announced the initiation of the Phase 1a portion of the clinical trial where we are evaluating the safety, tolerability and pharmacokinetic properties of NXP900 in patients with advanced solid tumors to identify potential doses and dosing schedules for the Phase 1b.

In the Phase 1b portion of the trial, we plan to investigate NXP900 in solid tumors where the SRC and/or YES1 pathways are overactivated and involved in the disease etiology.

Scientific Background

SRC is aberrantly activated in many cancer types, including solid tumor cancers such as breast, colon, prostate, pancreatic and ovarian cancers, while remaining predominantly inactive in non-cancerous cells.

Increased SRC activity is generally

associated with late-stage cancers, metastatic potential and resistance to therapies, and correlates with poor clinical prognosis.

Increased SRC activity is generally associated with late-stage cancers with metastatic potential and resistance to therapies and correlates with poor clinical prognosis.

To date, no kinase inhibitor has been approved for the treatment of SRC-active solid tumor malignancies.

6 unchanged sentences

NXP900 is a targeted-therapy that inhibits the SRC and YES1 kinases.

Unlike the approved and clinical-stage kinase inhibitors that inhibit only the catalytic (enzymatic) activity of SRC, NXP900 induces and locks SRC in its native inactive conformation by inhibiting both the catalytic and scaffolding functions of the kinase, thus preventing phosphorylation and complex formation with its primary partners.

Unlike the approved and clinical-stage kinase inhibitors that inhibit only the catalytic (enzymatic) activity of SRC, NXP900 induces and locks SRC in its native inactive conformation, therefore inhibiting both the catalytic and scaffolding functions of the kinase, thus preventing phosphorylation and complex formation with its primary partners.

NXP900 is also highly selective, a property typically associated with an improved therapeutic window.

In vivo, treatment with NXP900 inhibited primary and metastatic tumor growth in xenograft models of breast, cervical, esophageal, head and neck cancers and medulloblastoma, and demonstrated on-target pharmacodynamic effects.

Moreover, NXP900’s unique mechanism of action translated into substantial single-agent anti-cancer activity in several in vivo xenograft models.

Moreover, publications in the scientific literature outlined opportunities to potentially reverse resistance to osimertinib (Tagrisso ® ) in non-small cell lung cancer and enzalutamide (Xtandi ® ) in metastatic, castration resistant prostate cancer, in combination with these agents, validating the importance of NXP900’s key targets, YES1 and SRC kinases, in these disease settings.

In vivo, treatment with NXP900 inhibited primary and metastatic tumor growth in xenograft models of breast, esophageal, head and neck cancers and medulloblastoma, and demonstrated on-target pharmacodynamic effects.

Moreover, publications in the scientific literature outlined opportunities to potentially reverse resistance to osimertinib (active ingredient of Tagrisso®) in non-small cell lung cancer and enzalutamide (active ingredient of Xtandi®) in metastatic, castration resistant prostate cancer, in combination with these agents, validating the potential importance of NXP900’s key targets, YES1 and SRC kinases, in these disease settings.

Gene amplification of the site containing the YES1 gene has been reported in clinical samples in several tumors including lung, head and neck, bladder and esophageal cancers.

1 unchanged sentence

The transforming ability of YES1 has been demonstrated via several experimental methods, for example down-regulating YES1 by short hairpin RNA (shRNA) significantly inhibited cell growth in several malignancies, including colon carcinoma, rhabdomyosarcoma, and basal-like breast cancer suggesting YES1 may play a key role in these solid tumors.

Furthermore, it has been found that YES1 gene amplification is a key mechanism of resistance to Epidermal Growth Factor Receptor, Alk and Human Epidermal growth factor Receptor 2 inhibitors.

Furthermore, it has been found that YES1 gene amplification is a mechanism of resistance to epidermal growth factor receptor (“EGFR”), Anaplastic lymphoma kinase (“ALK”) and human epidermal growth factor receptor 2 (“HER2”) inhibitors.

There are no YES1 inhibitors that are FDA approved or currently in clinical development.

2 unchanged sentences

The key elements driving our business strategy include:

● advancing our lead product candidate, NXP800, through clinical development towards regulatory approval in platinum-resistant, ARID1a mutated ovarian carcinoma;

● maximizing the therapeutic potential for NXP800 in additional tumor types harboring the ARID1a-mutation, both as a monotherapy and possibly in combination with other approved therapies;

● positioning NXP900 as a potential differentiated YES1/SRC kinase inhibitor with improved therapeutic activity in solid tumors and advancing it through clinical development towards regulatory approval;

● maximizing the therapeutic potential of NXP900 by generating additional preclinical data to highlight the benefits of YES1 inhibition;

● advancing our lead product candidate, NXP800, through clinical development towards regulatory approval in platinum-resistant, ARID1a mutated ovarian carcinoma and cholangiocarcinoma;

● maximizing the therapeutic potential for NXP800 in additional tumor types, both as a monotherapy and possibly in combination with other approved therapies;

● developing NXP900 as a potential differentiated YES1/SRC kinase inhibitor with improved therapeutic activity in solid tumors and advancing it through clinical development towards regulatory approval;

● maximizing the therapeutic potential of NXP900 by generating additional preclinical data in single agent and combination settings to highlight the benefits of YES1 inhibition;

● deploying our differentiated and proven business development expertise to further expand our targeted oncology pipeline for patients with unmet medical needs;

13 unchanged sentences

Any issued patents that we may own or in-license in the future may be challenged, invalidated, circumvented, or have the scope of their claims narrowed.

Furthermore, the coverage claimed in a patent application can be significantly reduced before a patent is issued, and its scope can be reinterpreted and even challenged after issuance.

Furthermore, the coverage claimed in a patent

application can be significantly reduced before a patent is issued, and its scope can be reinterpreted and even challenged after issuance.

Moreover, many jurisdictions permit third parties to challenge issued patents in administrative proceedings, which may result in further narrowing or even cancellation of patent claims.

4 unchanged sentences

Patent and Trademark Office (“USPTO”) to determine priority of invention, which could result in substantial costs to us, even if the eventual outcome, which is highly unpredictable, is favorable to us.

expire or remain in force for only a short period following commercialization, thereby limiting the protection such patent would afford the respective product and any competitive advantage such patent may provide.

In addition, because of the extensive time required for clinical development and regulatory review of any current or future product candidates we may develop, it is possible that, before any current or future product candidates can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby limiting the protection such patent would afford the respective product and any competitive advantage such patent may provide.

In May 2021, we licensed one patent family covering the composition of matter for NXP800, which includes three issued U.S.

25 unchanged sentences

However, trade secrets can be difficult to protect.

Although we take steps to protect our proprietary information, including restricting access to our confidential information, as well as entering into non-disclosure and confidentiality agreements with our employees, consultants, independent contractors, advisors, contract manufacturers, clinical research organizations (“CROs”), hospitals, independent treatment centers, suppliers, collaborators and other third parties, such parties may breach such agreements and disclose our proprietary information including our trade secrets, and we may not be able to obtain adequate remedies for such breaches.

(“CROs”), hospitals, independent treatment centers, suppliers, collaborators and other third parties, such parties may breach such agreements and disclose our proprietary information including our trade secrets, and we may not be able to obtain adequate remedies for such breaches.

In addition, third parties may independently develop the same or similar proprietary information or may otherwise gain access to our proprietary information.

21 unchanged sentences

● mid-single digit to 8% royalties on a tiered basis based on net sales;

● 2.5% of the gross amount of each Nuvectis fundraising, including our initial public offering, up to an aggregate total of $3.0 million, of which $0.4 million has already been paid.

● 2.5% of the gross amount of each Nuvectis capital raising transaction, including our initial public offering, up to an aggregate total of $3.0 million, of which $0.8 million has already been paid.

In addition, in connection with the license agreement, we expect to provide the UoE with up to an additional £580,000 in research and development support over the next 18 months to conduct additional scientific research and preclinical testing for certain indications that we select in connection with the NXP900 Program.

13 unchanged sentences

There are several companies that are developing drugs for various types of ovarian cancer, including ImmunoGen, Inc.

and Constellation Pharmaceuticals, Inc.

(acquired by MorphoSys AG in June 2021).

(acquired by Abbvie Inc.

for $10.1B in February 2024) and MorphoSys AG (acquisition by Novartis AG pending).

MorphoSys AG disclosed patient recruitment commenced in May 2021 in a phase 2 expansion cohort for CPI-0209 in patients with relapsed urothelial carcinoma, relapsed OCCC, and relapsed endometrial carcinoma, all with known ARID1a mutations.

5 unchanged sentences

Turning Point Therapeutics, Inc.

(“Turning Point”) (Turning Point was Acquired by BMS in 4Q 2022 for $4.1 billion) is developing a MET/SRC/CSF1R inhibitor which is currently being studied in a Phase 1 trial of patients with advanced or metastatic solid tumors harboring Mesenchymal–Epithelial Transition kinase (“MET”) genetic alterations.

(“Turning Point”) (acquired by BMS in 4Q 2022 for $4.1 billion) is developing a MET/SRC/CSF1R inhibitor which is currently being studied in a Phase 1 trial of patients with advanced or metastatic solid tumors harboring Mesenchymal–Epithelial Transition kinase (“MET”) genetic alterations.

The simultaneous inhibition of MET, SRC and CSF1R kinases has been reported by Turning Point as a key component of the target product profile, and Turning Point has described the program as a strategy for the treatment of MET-driven solid tumors, an area that does not overlap with our development strategy.

Turning Point is also developing TPX-0046, a Rearranged during Transfection (“RET”) kinase inhibitor that can also inhibit other kinases including SRC family members, YES1, ABl, TRK and JAK2.

Turning Point is also developing enbezotinib (TPX-0046), a Rearranged during Transfection (“RET”) kinase inhibitor that can also inhibit other kinases including SRC family members, YES1, ABl,

TRK and JAK2.

TPX-0046 is being evaluated in an ongoing Phase 1/2 clinical trial for the treatment of advanced solid tumors with RET gene alterations, an area that does not overlap with our development strategy.

3 unchanged sentences

In addition, we may need to develop our current or future product candidates in collaboration with diagnostic companies, and we will face competition from other companies in establishing these collaborations.

Our competitors will also compete with us in recruiting and retaining qualified scientific, management and commercial personnel, establishing clinical trial

sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

Our competitors will also compete with us in recruiting and retaining qualified scientific, management and commercial personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

For a description of these risks, please see the section entitled “Risk Factors.”

5 unchanged sentences

We do not lease or own any manufacturing facilities.

We currently rely, and expect to continue to rely, on third-party manufacturers, including a single, sole source manufacturer to make the NXP800 drug substance and finished drug product, each done at a different manufacturing facility.

We rely on a single, sole source manufacturer to make the NXP900 drug substance and another single, sole source manufacturer to make the NXP900 finished drug product.

Prior to commencing the Phase 1 clinical trial for NXP900, we, and the third-party drug product manufacturer on our behalf, will need to meet the full-clinical scale current Good Manufacturing Practices ("cGMPs") requirements for the manufacturing of the NXP900 drug product and we plan to complete this in the near future.

However, there is no assurance that we will be able to successfully do so.

With any supply program, obtaining raw materials of the correct quality cannot be guaranteed and we cannot ensure that we will be successful in these endeavors.

We currently rely, and expect to continue to rely, on third-party manufacturers for the production of drug substance and drug product for clinical trials in accordance with current Good Manufacturing Practices ("cGMPs"), including a single, sole source manufacturer to make the NXP800 drug substance and finished drug product, each performed at a different manufacturing facility, and a single, sole source manufacturer to make the NXP900 drug substance and another single, sole source manufacturer to make the NXP900 finished drug product.

There is no assurance that we will be able to successfully manufacture drug substance and/or drug product for NXP800 and/or NXP900.

As with any supply program, obtaining raw materials of the correct quality cannot be guaranteed and we cannot ensure that we will be successful in these endeavors.

We plan to continue to rely on third-party manufacturers for the supply of NXP800 and NXP900, for manufacture of future additional product candidates, for preclinical testing as well as for clinical trials and commercial manufacture if our current or future product candidates receive marketing approval.

4 unchanged sentences

If we fail to comply with applicable FDA or other legal requirements, we may become subject to administrative or judicial sanctions or other legal consequences.

These sanctions or consequences may include, among other things, the FDA’s denial of our pending applications, the issuance of clinical holds for ongoing studies, suspension or revocation of approved applications, warning or untitled letters, product withdrawals or recalls, product seizures, relabeling or repackaging, total or partial suspensions of manufacturing or distribution, injunctions, fines, civil penalties or criminal prosecution.

These sanctions or consequences may include, among other things, the

FDA’s denial of our pending applications, the issuance of clinical holds for ongoing studies, suspension or revocation of approved applications, warning or untitled letters, product withdrawals or recalls, product seizures, relabeling or repackaging, total or partial suspensions of manufacturing or distribution, injunctions, fines, civil penalties or criminal prosecution.

The clinical testing and approval processes require substantial time, effort, and financial resources, and we cannot be certain that any approvals for our current or future product candidates will be granted on a timely basis, if at all.

28 unchanged sentences

A new drug is eligible for Fast Track Designation if it is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address an unmet medical need for such disease or condition.

Fast track Designation

provides increased opportunities for sponsor interactions with the FDA during preclinical and clinical development, in addition to the potential for rolling review of a marketing application once a marketing application is filed, meaning that the agency may review portions of the application before the sponsor submits the complete application, as well as priority review, discussed below.

Fast Track Designation provides increased opportunities for sponsor interactions with the FDA during preclinical and clinical development, in addition to the potential for rolling review of a marketing application once a marketing application is filed, meaning that the agency may review portions of the application before the sponsor submits the complete application, as well as priority review, discussed below.

In December 2022, we announced that the FDA granted Fast Track Designation status to NXP800 for the treatment of patients with platinum-resistant, ARIDA1a-mutated ovarian carcinoma.

15 unchanged sentences

Healthcare providers, physicians, and third-party payors will play a primary role in the recommendation and prescription of any products for which we obtain marketing approval.

Our business operations and any current or future arrangements

with third-party payors, healthcare providers and physicians may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we develop, market, sell and distribute any drugs for which we obtain marketing approval.

Our business operations and any current or future arrangements with third-party payors, healthcare providers and physicians may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we develop, market, sell and distribute any drugs for which we obtain marketing approval.

In the United States, these laws include, without limitation, state and federal anti-kickback, false claims, physician transparency, and patient data privacy and security laws and regulations.

14 unchanged sentences

We may be subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes.

From time to time and in the future, our operations may involve the use of hazardous and flammable materials, including chemicals and biological materials, and may also produce hazardous waste products.

From time to time and in the future, our operations may involve the use of hazardous and flammable materials, including chemicals

and biological materials, and may also produce hazardous waste products.

Even if we contract with third parties for the disposal of these materials and waste products, we cannot completely eliminate the risk of contamination or injury resulting from these materials.

17 unchanged sentences

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