8-K: Traws Pharma Reveals Compelling Rigosertib Efficacy in Rare Skin Cancer, Seeks Partners for Oncology Assets

Traws Pharma, a biopharmaceutical company primarily focused on respiratory viral diseases, announced highly positive clinical efficacy data for its legacy oncology drug, rigosertib, in patients with recessive dystrophic epidermolysis bullosa associated squamous cell carcinoma (RDEB-SCC), while also highlighting its narazaciclib program and the company's intent to find development and commercialization partners for both assets.

Summary

• Traws Pharma announced the publication of clinical efficacy data for rigosertib in an investigator-sponsored, open-label, single-arm Phase 2 study for recessive dystrophic epidermolysis bullosa associated locally advanced or metastatic squamous cell carcinoma (RDEB-SCC) patients.
• The study results indicated an overall response rate of 80% with complete responses in 50% of evaluable RDEB-SCC patients, a disease with substantial unmet need and no approved therapies.
• Rigosertib is a small molecule kinase inhibitor, including PLK-1, and has a clinical safety database of over 1300 patients in cancer.
• Traws Pharma is actively seeking development and commercialization partners for its legacy oncology programs, rigosertib and narazaciclib.
• Narazaciclib, another legacy oncology asset, is a multi-targeted CDK4/6 inhibitor that also inhibits ARK5 and CSF1R, designed to overcome resistance challenges of current approaches.
• Preclinical data for narazaciclib support activity in CDK4/6-refractory breast cancer and show reduced neutropenia and diarrhea compared to existing CDK4/6 inhibitors.
• Phase 1 studies for narazaciclib have established a recommended Phase 2 dose (RP2D) of 160 mg in combination with Letrozole, and monotherapy dose escalation reached 280mg with a favorable safety profile.
• Some patients in narazaciclib monotherapy studies showed prolonged stable disease (SD) for up to 413 days.
• Two investigator-sponsored studies for narazaciclib (metastatic HR+ breast cancer and relapsed refractory multiple myeloma) are currently on hold, pending funding.

Sentiment

Score: 7

Explanation: The sentiment is positive due to the highly compelling clinical efficacy data for rigosertib in a rare, high-unmet-need cancer and the differentiated profile of narazaciclib. However, this is tempered by the fact that these are 'legacy' programs for which Traws is seeking partners, and some narazaciclib studies are on hold pending funding, indicating potential capital constraints and a shift in company focus.

Positives

• Rigosertib demonstrated a compelling overall response rate of 80% and complete responses in 50% of evaluable patients in a Phase 2 study for RDEB-SCC, a highly aggressive and difficult-to-treat rare cancer.
• RDEB-SCC has a substantial unmet need with no currently approved treatments globally, making rigosertib's efficacy particularly significant.
• Narazaciclib is a differentiated CDK4/6+ inhibitor that targets additional kinases like ARK5 and CSF1R, which are implicated in resistance mechanisms and immune evasion, potentially overcoming limitations of current therapies.
• Preclinical data for narazaciclib suggest a more favorable safety profile with reduced neutropenia and diarrhea compared to palbociclib, and activity in palbociclib-resistant cell lines.
• Narazaciclib Phase 1 studies have established a recommended Phase 2 dose in combination with Letrozole and shown early signs of promising activity, with some patients achieving prolonged stable disease for over a year.

Negatives

• Traws Pharma is actively seeking development and commercialization partners for both rigosertib and narazaciclib, indicating these oncology programs are not the company's primary focus.
• Two investigator-sponsored studies for narazaciclib (in metastatic HR+ breast cancer and relapsed refractory multiple myeloma) are currently on hold, pending funding, which could delay further development.
• The company explicitly states risks related to its ability to obtain sufficient additional capital to continue to advance its product candidates and operate its business.

Risks

• Uncertainties associated with Traws' product candidates, including risks related to clinical development and regulatory approval, and potential delays in trials.
• Risks related to Traws' ability to identify and solidify partnerships for the advancement of certain product candidates.
• Risks related to Traws' ability to obtain sufficient additional capital to continue to advance its product candidates and operate its business.
• Uncertainties in obtaining successful clinical results for product candidates and unexpected costs that may result therefrom.
• Risks related to the failure to realize any value from product candidates currently being developed.
• Uncertainties in retaining key personnel, including the executive team and directors.
• Risks that may stem from changes in the regulatory and/or political landscape.
• Risks associated with the possible failure to realize certain anticipated benefits of Traws' 2024 merger with Trawsfynydd Therapeutics, Inc.

Future Outlook

Traws Pharma is actively seeking development and commercialization partners for its legacy oncology programs, rigosertib and narazaciclib, to advance these medicines to approval. The company anticipates further clinical development activities, related timelines, and interactions with regulatory bodies, subject to securing partnerships and additional funding. Future results are based on management's best estimates and current conditions.

Management Comments

• Victor Moyo, MD, Chief Medical Officer Oncology, Traws Pharma: "We are excited to report the compelling efficacy and tolerability profile of rigosertib in this devastating, difficult to treat disease, and thank the patients, sponsors and investigators for their commitment to this program."
• Iain Dukes, MA, DPhil, Interim CEO, Traws Pharma: "Rigosertib is available for further development and commercialization, and we are committed to finding an appropriate partner to advance this important medicine to approval."

Industry Context

The announcement highlights Traws Pharma's efforts in oncology, particularly in rare and difficult-to-treat cancers like RDEB-SCC, where there is a significant unmet medical need and limited treatment options. The focus on a multi-targeted CDK4/6 inhibitor like narazaciclib addresses the growing challenge of resistance in metastatic breast cancer, a major area of research and development in the oncology industry. The company's strategy to seek partners for these legacy assets suggests a shift towards its core focus on respiratory viral diseases, aligning with a trend where smaller biotechs may out-license promising assets to larger pharmaceutical companies for broader development and commercialization.

Comparison to Industry Standards

• Rigosertib's 80% overall response rate and 50% complete response rate in RDEB-SCC are highly favorable compared to current treatment regimens for this aggressive disease, which typically produce limited response rates and poor durability.
• Narazaciclib differentiates itself from other CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib by also inhibiting ARK5 and CSF1R, which are key kinases implicated in resistance mechanisms and immune evasion, offering a potential advantage in overcoming resistance.
• Preclinical data suggest narazaciclib has a reduced incidence of neutropenia and diarrhea compared to palbociclib, potentially offering a more tolerable safety profile than existing CDK4/6 inhibitors.
• The licensing deal of RGT-419B (a CDK4+ inhibitor) by Regor Therapeutics to Roche for $850 million upfront in October 2024 provides a benchmark for the potential value of differentiated CDK inhibitors, suggesting narazaciclib, with its broader kinase inhibition profile (CSF-1R and ARK5, which RGT-419B does not target), could also attract significant partnership interest.

Management Changes

Stakeholder Impact

• Shareholders: Potential positive impact from strong rigosertib data and potential partnerships, but also uncertainty from funding needs and the 'legacy' status of oncology programs.
• Patients (RDEB-SCC): Significant positive impact due to rigosertib's compelling efficacy in a devastating disease with no approved therapies, offering hope for a new treatment option.
• Patients (HR+/HER2mBC): Potential future benefit from narazaciclib's differentiated mechanism, especially for those who have progressed on existing CDK4/6 inhibitors, though current funding delays are a concern.
• Investment Professionals: Provides critical data for evaluating Traws Pharma's oncology pipeline and strategic direction, particularly regarding partnership opportunities and capital needs.

Next Steps

• Traws Pharma will continue actively seeking development and commercialization partners for rigosertib and narazaciclib.
• Further clinical development of rigosertib in RDEB-SCC is planned, with a proposed 2-arm multi-country, multi-center Phase II study (sample size 12-20 patients) subject to regulatory meetings.
• Data analysis is ongoing for completed narazaciclib studies in low grade endometrial endometrioid carcinoma and solid tumors.
• Resumption of narazaciclib studies currently on hold (metastatic HR+ breast cancer and relapsed refractory multiple myeloma) is pending funding.

Key Dates

Recommendation

Keywords

Rigosertib, Narazaciclib, Oncology, RDEB-SCC, Squamous Cell Carcinoma, Metastatic Breast Cancer, CDK4/6 Inhibitor, Biopharmaceutical, Clinical Trials, Rare Disease, Drug Development, Partnership, SEC Filing