On January 13, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported it will share corporate progress and highlights from the Company’s broad and diverse investigational pipeline while presenting at the annual J.P. Morgan Healthcare Conference (Press release, Regeneron, JAN 13, 2025, View Source [SID1234649674]). The presentation is scheduled for 2:15 p.m. Pacific Time (5:15 p.m. Eastern Time) and may be accessed from the "Investors & Media" page of Regeneron’s website.

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"The Regeneron name is synonymous with innovation, brought to life through proprietary technologies and world-class science that produce medicines that make a meaningful impact on patients’ lives," said Leonard S. Schleifer, M.D., Ph.D., Board co-Chair, President and Chief Executive Officer of Regeneron. "Thanks to our long-term and consistent R&D investment, we have – in addition to our four blockbuster medicines – one of the industry’s largest, most promising and most diverse clinical pipelines. Our therapeutic candidates tackle a myriad of diseases, with the most advanced programs addressing an aggregate commercial market opportunity expected to exceed $220 billion by 2030. We are well positioned for future growth and more confident than ever in the power of Regeneron’s science."

Marketed Products

Dupixent Updates

Dupixent (dupilumab) is now used to treat over a million patients globally. The recent approval and launch in chronic obstructive pulmonary disease (COPD) has had a successful start, with coverage secured from the top commercial and Medicare payers and Dupixent now well positioned to address approximately 300,000 patients in the U.S.
There is continued growth potential in existing and additional indications for diseases in which type 2 inflammation may play a role, including chronic spontaneous urticaria (CSU) with an expected U.S. Food and Drug Administration (FDA) decision by April 18, 2025, and bullous pemphigoid, for which a supplemental Biologics License Application (sBLA) was submitted in the fourth quarter of 2024.
EYLEA HD and EYLEA Updates

On a combined basis, EYLEA HD (aflibercept) Injection 8 mg and EYLEA (aflibercept) Injection 2 mg remained the U.S. anti-VEGF category leader in 2024. Based on preliminary (unaudited) results, the products achieved 1% year-over-year growth by reaching $6 billion in aggregate U.S. net product sales for the year and $1.5 billion in aggregate U.S. net product sales for the fourth quarter of 2024, despite increasing competition. EYLEA HD U.S. net product sales were $305 million in the fourth quarter of 2024. EYLEA U.S. net product sales were $1.19 billion in the fourth quarter of 2024.
Combined EYLEA HD and EYLEA U.S. net product sales for the fourth quarter of 2024 were favorably impacted by approximately $85 million as a result of higher wholesaler inventory levels for EYLEA, partially offset by lower wholesaler inventory levels for EYLEA HD.
The Company filed an application with the FDA for use of the EYLEA HD pre-filled syringe (PFS) with U.S. approval and launch expected by mid-2025.
Longer term data in wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) are under FDA review with a PDUFA date of April 20, 2025 to potentially extend dosing intervals for EYLEA HD up to every-24 weeks.
The Company plans to submit a sBLA for EYLEA HD for every four-week dosing and for retinal vein occlusion (RVO) in the first quarter of 2025 to potentially maximize dosing flexibility and address more retinal diseases.

Libtayo Updates

Libtayo (cemiplimab) exceeded $1 billion in sales for 2024 and remains foundational to Regeneron’s oncology portfolio.
As announced this morning, a Phase 3 study demonstrated that Libtayo is the only immunotherapy to show a statistically significant and clinically meaningful benefit in high-risk cutaneous squamous cell carcinoma (CSCC) in the adjuvant setting; a recent Phase 3 trial with Keytruda failed in the same setting.1 Specifically, adjuvant Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death, compared to placebo (hazard ratio: 0.32; 95% confidence interval: 0.20-0.51; p<0.0001). Grade ≥3 adverse events occurred in 24% (n = 49 of 205) and 14% (n = 29 of 204) of patients in the Libtayo arm and the placebo arm, respectively. Detailed results will be presented at an upcoming medical meeting and will be shared with regulatory authorities with a plan for FDA submission in the first half of 2025.
Phase 3 and Other Major Pipeline Opportunities

Regeneron is progressing numerous promising drug candidates across diverse disease states, with advanced programs that together have a total addressable commercial market expected to exceed $220 billion by 2030. Some near-term highlights include:

Itepekimab (IL-33) for COPD: Based on genetic data linking IL-33 with increased risk of COPD and Phase 2 results, Regeneron’s next innovation in COPD offers potential for benefit in a broader population, including former smokers, non-cystic fibrosis bronchiectasis and other indications. Results are expected from the Phase 3 AERIFY study in the second half of 2025, with a potential BLA submission to follow.

Fianlimab (LAG3) for melanoma: Combining fianlimab and Libtayo, two potentially best-in-class checkpoint inhibitors, has the potential for differentiated efficacy and safety versus the current standard-of-care. Results from the first Phase 3 study in first-line metastatic melanoma are expected in the second half of 2025, with a potential BLA submission to follow.

Linvoseltamab (BCMAxCD3) for multiple myeloma: Linvoseltamab has potential to be the best-in-class BCMAxCD3 bispecific with its differentiated clinical profile, dosing regimen and administration method. The linvoseltamab BLA has been resubmitted following resolution of third-party manufacturing issues, with launch anticipated in mid-2025. Phase 3 programs in earlier lines of therapy using linvoseltamab monotherapy and novel combinations are also underway.

Odronextamab (CD20xCD3) for lymphoma: Ordspono (odronextamab) has been approved in the European Union for relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy, and enrollment is underway for a confirmatory study to support resubmission of the BLA for FL to the FDA in the first quarter of 2025. A broad and differentiated Phase 3 program is also underway to investigate odronextamab in earlier lines of FL and DLBCL. As reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting, odronextamab monotherapy showed complete responses in 12 out of 12 evaluable patients with first-line FL in the safety lead-in portion of the Phase 3 program.

Factor XI for anticoagulation: Regeneron’s two-pronged approach to anticoagulation is being evaluated for its potential to control thombosis while minimizing bleeding risk in a variety of patient populations and clinical settings. Two Factor XI antibodies, REGN7508 (catalytic domain) and REGN9933 (A2 domain), will advance to pivotal trials in 2025 on the basis of positive proof-of-concept data announced in December 2024. Current standards of care for thrombosis disorders have challenges including elevated risk of bleeding resulting in underutilization, presenting an unmet need for more specific inhibition of the intrinsic coagulation pathway.

Multiple approaches to obesity: Regeneron is studying various combinations with GLP-based therapies to potentially improve quality of weight loss by preserving lean muscle, as well as improve maintenance of weight loss following GLP-1/GIP discontinuations. A Phase 2 study of trevogrumab and semaglutide with and without garetosmab is now fully enrolled and a Phase 2 study testing combinations of tirzepatide and mibavademab is ongoing, with initial data expected from both in the second half of 2025.

BCMAxCD3/Dupixent in severe allergy: Combining linvoseltamab and Dupixent has the potential to eliminate immunoglobulin E (IgE), the key driver of allergic reactions, and thus potentially reverse severe allergies. A trial in patients with severe food allergies is ongoing, with initial clinical data shared in today’s presentation showing profound reduction of IgE in the first patient treated with this two-drug approach.

C5 Combo (pozelimab and cemdisiran) in complement-mediated diseases: Regeneron’s differentiated siRNA and antibody combination approach has the potential to address multiple complement-mediated diseases, such as generalized myasthenia gravis (Phase 3 results expected in the second half of 2025), paroyxsmal noctural hemoglobinuria (Phase 3 registrational data expected in 2026+) and geographic atrophy, an advanced form of dry AMD (Phase 3 pivotal program underway).

DNA Sequence-Linked Healthcare Database

Regeneron continues to grow its leadership in genetics-driven drug discovery and is building the world’s largest DNA sequence-linked healthcare database, designed to unlock profound insights into how genetics impact health and aid in the development new genetic-based therapies and optimized healthcare services.

The Regeneron Genetics Center has sequenced nearly three million people to date, all with deidentified linked healthcare records.
A newly announced strategic collaboration with Truveta, Inc. is expected to dramatically expand the size of this database, with sequencing and linked Electronic Health Records for up to 10 million additional individuals from Truveta’s network of leading U.S. health systems.
On the basis of its industry-leading capabilities, Regeneron Genetics Center was selected by UK BioBank consortium members to complete proteomic assay data generation for the recently announced UK Biobank Pharma Proteomics Project.

"Regeneron continues to diversify our commercial, clinical and research portfolios by relentlessly pushing the boundaries of innovation and technology," said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer of Regeneron. "In 2025, we will progress dozens of promising new assets and expand the reach of our important established medicines to help even more patients in need. We remain at the forefront of biotechnology’s most remarkable era of drug discovery, striving to change the practice of medicine with approaches spanning antibodies, bispecifics, gene editing, gene silencing, gene therapy and cell therapy supported by DNA sequence- and proteomics-linked healthcare database."

The unapproved uses of EYLEA, EYLEA HD, Dupixent, Libtayo and pozelimab noted here are investigational and have not been fully evaluated by any regulatory authority. Cemdisiran, itepekimab, fianlimab, linvoseltamab, REGN7508, REGN9933, trevogrumab and garetosmab are investigational and have also not been fully evaluated by any regulatory authority. Odronextamab is approved in the European Union as Ordspono to treat R/R FL or DLBCL after two or more lines of systemic therapy, but the safety and efficacy of odronextamab has not been fully evaluated by any other regulatory authority.

On January 13, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported positive results from the Phase 3 C-POST trial, which demonstrated that adjuvant treatment with PD-1 inhibitor Libtayo (cemiplimab) led to a statistically significant and clinically meaningful improvement in the primary endpoint of disease-free survival (DFS) in patients with high-risk cutaneous squamous cell carcinoma (CSCC) after surgery (Press release, Regeneron, JAN 13, 2025, View Source [SID1234649673]).

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"While surgery is curative for most people living with cutaneous squamous cell carcinoma, many are burdened with a higher risk of recurrence that can lead to death or disfiguration," said Danny Rischin, M.D., M.B.B.S., F.R.A.C.P., Research Lead, Head and Neck Cancer and Cutaneous SCC, Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, and lead investigator of the trial. "At the first prespecified interim analysis, Libtayo achieved a remarkably high bar in improving disease-free survival in high-risk cutaneous squamous cell carcinoma. With no currently approved options in the adjuvant setting, these landmark results demonstrate Libtayo could represent a major advance in delaying recurrence in these vulnerable patients."

C-POST enrolled 415 patients with high-risk CSCC who were randomized to receive either Libtayo or placebo for up to 48 weeks. The primary endpoint was DFS, defined as time from randomization to the first documented disease recurrence or death due to any cause. At the first prespecified interim analysis for DFS with a median duration of follow-up of 24 months (range: 2-64 months), Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death, compared to placebo (hazard ratio: 0.32; 95% confidence interval: 0.20-0.51; p<0.0001).

Safety was assessed in 205 patients in the Libtayo arm and 204 patients in the placebo arm. Adverse events (AEs) of any grade occurred in 91% and 89% of patients in the Libtayo arm and the placebo arm, respectively. Grade ≥3 AEs occurred in 24% and 14% of patients in the Libtayo arm and the placebo arm, respectively. Treatment discontinuations due to adverse reactions occurred in 10% and 1.5% of patients in the Libtayo arm and the placebo arm, respectively. Two patients experienced an AE leading to death in each arm.

Following these interim results, C-POST will continue for additional follow-up, including an analysis of the key secondary endpoint of overall survival. Detailed results will be presented at an upcoming medical meeting and will be shared with regulatory authorities with a plan for U.S. Food and Drug Administration (FDA) submission in the first half of 2025.

"Regeneron has long been a pioneer in non-melanoma skin cancer research. Libtayo was the first PD-1 inhibitor approved for certain patients with advanced cutaneous squamous cell carcinoma and has become a standard of care in this setting," said Israel Lowy, M.D., Ph.D., Clinical Development Unit Head, Oncology, at Regeneron. "With these results, Libtayo now has the potential to also transform the treatment of high-risk resectable cutaneous squamous cell carcinoma with adjuvant treatment. This trial is a testament to our unrelenting commitment to investigating areas where patient need remains high and to pursuing clinical research across diverse stages of skin cancer."

The potential use of Libtayo described above is investigational, and its safety and efficacy has not been evaluated by any regulatory authority for this indication.

About the Phase 3 Trial
C-POST is an ongoing randomized, placebo-controlled, double-blind, multicenter, global Phase 3 trial investigating Libtayo versus placebo as adjuvant treatment for patients with features associated with a high-risk of CSCC recurrence and who have completed surgery and post-operative radiation therapy. Trial participants are at high risk of recurrence due to nodal features (extracapsular extension or ≥3 involved lymph nodes) and/or non-nodal features (in-transit metastases, T4 lesion, perineural invasion, or locally recurrent tumor with ≥1 additional poor prognostic features).

For the first 12 weeks, Libtayo 350 mg or placebo is administered intravenously every three weeks, followed by Libtayo 700 mg or placebo administered intravenously every six weeks for 36 weeks. The primary endpoint is DFS, and the secondary endpoints include freedom from locoregional recurrence, freedom from distant recurrence, overall survival, cumulative incidence of second primary CSCC tumors, and safety.

The Trans-Tasman Radiation Oncology Group (TROG), with Dr. Rischin as lead investigator, collaborated with Regeneron on protocol development. Trial sites included 24 TROG sites in Australia.

On January 13, 2025 Rakovina Therapeutics Inc. (TSX-V: RKV), a biopharmaceutical company dedicated to advancing new cancer therapies based on novel DNA-damage response technologies, reported the successful achievement of a shortlist of AI-generated molecules targeting ATR (Ataxia Telangiectasia and Rad3-related protein) with specific designs for central nervous system (CNS) penetration (Press release, Rakovina Therapeutics, JAN 13, 2025, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-announces-key-milestone-in-cancer-drug-innovation-in-collaboration-with-variational-ai [SID1234649672]).

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This milestone represents the first significant deliverable in Rakovina’s partnership with Variational AI, which leverages their state-of-the-art Enki platform to fast-track the discovery of innovative inhibitors for specific DNA damage response (DDR) kinase targets. ATR is an important drug target due its critical involvement in the DNA damage response (DDR). Its inhibition can lead to selective cancer cell death and improved therapeutic outcomes when combined with other treatments.

These new ATR-targeted inhibitors will now advance to chemical synthesis followed by preclinical validation, a critical step in Rakovina’s mission to address unmet medical needs in oncology.

Innovative Approach to Drug Discovery

The shortlisted molecules were developed using Variational AI’s proprietary Enki foundation model platform to generate novel chemical compounds from the estimated 1060 molecules in chemical space, far greater than any screening library. The platform identifies promising drug candidates while reducing timelines from years to just months. With CNS penetration capabilities, these molecules are poised to address cancers that metastasize to the brain or originate within the CNS, areas with historically limited treatment options.

This achievement is just the beginning of a dynamic journey. Rakovina is broadening its research scope with Variational AI to target additional DDR kinase pathways, with the vision of building a comprehensive pipeline of next-generation small-molecule therapies. By leveraging generative AI, the Company can eliminate traditional barriers, promising a new era of faster, more precise cancer treatment development.

"We are pleased to announce the achievement of this first milestone in our collaboration with Variational AI," said Jeffrey Bacha, Executive Chairman of Rakovina Therapeutics. "The identification of ATR-targeted drug candidates with CNS penetration exemplifies the transformative potential of AI in cancer therapy. This progress represents a meaningful step forward in our research and demonstrates the growing impact of AI in accelerating drug development and innovation in oncology."

On January 13, 2025 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported recent updates and anticipated 2025 milestones (Press release, Protara Therapeutics, JAN 13, 2025, View Source [SID1234649671]).

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"Following a highly productive 2024 marked by positive data in our non-muscle invasive bladder cancer (NMIBC) program and with the funds from a successful financing, we are well positioned to accelerate our development programs and deliver on our mission to provide novel therapies to patients impacted by cancer and rare diseases," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "Looking ahead, we expect several key milestones in 2025, including reporting data on 12-month evaluable patients in our ADVANCED-2 trial of TARA-002 in NMIBC mid-year. On the heels of our recently reported positive interim data from six-month evaluable patients, we continue to believe that TARA-002 could represent a meaningful and differentiated addition to the NMIBC treatment paradigm with an attractive product profile for both physicians and patients."

"In addition, we expect to begin the pivotal THRIVE-3 study of intravenous (IV) Choline Chloride in the first half of 2025. We also expect data from our ongoing Phase 2 STARBORN-1 trial of TARA-002 in lymphatic malformations (LMs) by the end of the first half of 2025."

Recent Company Updates and Planned 2025 Milestones

TARA-002 in NMIBC

In December 2024, the Company reported positive interim results from its ongoing Phase 2 open-label ADVANCED-2 trial in in NMIBC patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive and BCG-Naïve at the 25th Annual Meeting of the Society of Urologic Oncology (SUO) in Dallas, Texas. The complete response (CR) rate across BCG exposures was 72% (13/18) at six months and 70% (14/20) at any time, with 100% (9/9) of patients maintaining a CR from three months to six months. In addition, two of three patients maintained a CR at nine months. TARA-002 showed a favorable safety profile, with no Grade 2 or greater treatment-related adverse events and no treatment discontinuations due to adverse events.
The Company expects to report data on 12-month evaluable patients in the ADVANCED-2 trial in mid-2025 and results from a futility analysis of approximately 25 six-month evaluable BCG-Unresponsive patients are expected by the end of 2025. As previously announced, the BCG-Unresponsive cohort is designed to be registrational in alignment with the 2024 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment Draft Guidance for Industry issued by the U.S. Food and Drug Administration (FDA).
The Company expects to provide an update on the design of its planned BCG-Naïve registrational trial by the end of the first half of 2025 following regulatory alignment.
The Company continues to explore the administration of systemic priming dosing prior to initiation of intravesical administration, as well as combination therapy with TARA-002 in NMIBC patients with CIS. Given TARA-002’s mechanism of action and safety profile, the Company believes it has strong potential for use in combination therapy and is working to finalize various opportunities for the clinical program.
IV Choline Chloride for Patients on Parenteral Support (PS)

The Company expects to commence the THRIVE-3 registrational trial of IV Choline Chloride, an investigational phospholipid substrate replacement, in adolescents and adults on long-term PS when oral or enteral nutrition is not possible, insufficient, or contraindicated, in the first half of 2025. IV Choline Chloride was previously granted Fast Track designation by the FDA as a source of choline for this patient population.
In September 2024, the Company announced results from THRIVE-1, a prospective, observational study, which found that 78% of PS-dependent patients were choline deficient, and 63% of these patients demonstrated liver dysfunction, including steatosis, cholestasis, and hepatobiliary injury.
TARA-002 in LMs

Protara remains on track to report initial results from additional cohorts in the Phase 2 STARBORN-1 trial of TARA-002 in pediatric patients with macrocystic and mixed cystic LMs by the end of the first half of 2025. The Company previously announced completion of the study’s first safety cohort, in which TARA-002 demonstrated encouraging efficacy and was generally well-tolerated.
Financial Guidance

The Company today provided updated financial guidance. Protara believes its approximately $81.5 million of cash, cash equivalents, and investments in marketable debt securities as of September 30, 2024, together with approximately $100 million gross proceeds from its December 2024 public offering, will be sufficient to fund its planned operations into 2027.

On January 13, 2025 Phio Pharmaceuticals Corp. (Nasdaq: PHIO) is a clinical-stage biotechnology company developing therapeutics that use its INTASYL siRNA gene silencing technology designed to make the body’s immune cells more effective in killing cancer cells (Press release, Phio Pharmaceuticals, JAN 13, 2025, View Source [SID1234649670]). Phio reported pathologic responses for patients enrolled in the 2nd cohort, which includes 2 patients with a complete response or 100% tumor clearance.

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Phio’s ongoing Phase 1b clinical study (NCT 06014086) is designed to evaluate the safety and tolerability of neoadjuvant use of intratumoral PH-762 in Stages 1, 2 and 4 cutaneous squamous cell carcinoma, Stage 4 melanoma and Stage 4 Merkel cell carcinoma.

Of the patients enrolled to date, 6 patients were diagnosed with cutaneous squamous cell carcinoma and 1 patient was diagnosed with metastatic melanoma. At Day 36 (tumor excision), while patients in the first cohort had stable disease, results are now available for the 4 patients who completed treatment in the 2nd cohort:

· Complete response (100% tumor clearance) is reported for 2 patients with cutaneous squamous cell carcinoma. Partial response (90% tumor clearance) is reported for 1 patient with cutaneous squamous cell carcinoma and 1 patient had stable disease, having not progressed.

There have been no dose-limiting toxicities, or clinically relevant treatment-emergent adverse events in the patients receiving intratumoral PH-762. The intratumoral injections have been well tolerated.

"We are pleased and encouraged by the profound tumor response in the second dose cohort, coupled with reassuring safety data," said Mary Spellman MD, Phio’s acting Chief Medical Officer. "We look forward to continued enrollment which will permit assessment of higher dose concentrations of PH-762."

"These positive results in the early stages of dose escalation offer promise for our vision, ‘striving for a cancer free future’ using INTASYL technology" said Robert Bitterman, CEO of Phio Pharmaceuticals.