On February 12, 2025 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, reported financial results for the fiscal third quarter ended December 31, 2024 and provided a business update (Press release, Replimune, FEB 12, 2025, View Source [SID1234650211]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Over the past couple of months, we have achieved significant regulatory milestones for RP1 in anti-PD-1 failed melanoma," said Sushil Patel, Ph.D., CEO of Replimune. "With Priority Review and a PDUFA date set for July 22, 2025, by the FDA, our efforts are focused on ensuring a successful commercial launch of RP1 upon approval. Our commercial strategy is built on a deep understanding of the patient population and prescriber landscape, coupled with a launch model designed to effectively deliver intratumoral therapy. With over $500 million in cash, we are well-capitalized to execute our plans and are excited to provide further updates as we transition to a commercial-stage company."

Program Highlights & Milestones

RP1

RP1 combined with Opdivo (nivolumab) in anti-PD1 failed melanoma
In January, the FDA accepted the BLA for RP1 in combination with nivolumab for patients with advanced melanoma. The BLA was granted Priority Review by the FDA with a PDUFA action date of July 22, 2025.
The BLA is supported by the primary analysis data of the IGNYTE trial, evaluating RP1 combined with nivolumab in patients with anti-PD-1 failed melanoma.
Enrolling into the confirmatory Phase 3 trial, IGNYTE-3, with over 100 sites planned globally. This trial will assess RP1 in combination with nivolumab in patients with advanced melanoma who have progressed on anti-PD-1 and anti-CTLA-4 therapies or are ineligible for anti-CTLA-4 treatment.
RP2

RP2 in uveal melanoma
Enrolled the first patient in a registration-directed study of RP2 in metastatic uveal melanoma in patients who are immune checkpoint inhibitor-naïve. The study will enroll approximately 280 patients and evaluate RP2 in combination with nivolumab versus ipilimumab in combination with nivolumab. The primary endpoints of the study are overall survival and progression free survival and key secondary endpoints are overall response rate and disease control rate.
RP2 in hepatocellular carcinoma (HCC)
Enrolled the first patient in a Phase 2 clinical trial with RP2 combined with atezolizumab and bevacizumab in anti-PD1/PD-L1 progressed HCC. The trial is an open label trial that will enroll 30 patients and evaluate RP2 combined with the second-line therapy of atezolizumab and bevacizumab. The study is being conducted under a collaboration and supply agreement with Roche.
Financial Highlights

Financing: Completed a public offering of shares of the Company’s common stock and pre-funded warrants, raising approximately $156.0 million net of issuance costs. Proceeds from the financing will be used to fund the continued development of our RPx platform, including expanding our ongoing studies within RP1 and broadening clinical development plans for RP2, as well as for working capital and general corporate purposes.
Cash Position: As of December 31, 2024, cash, cash equivalents and short-term investments were $536.5 million, as compared to $420.7 million as of fiscal year ended March 31, 2024. The increase in cash balance was directly related to the public offering in November, somewhat offset by cash utilized in operating activities in advancing the Company’s clinical development plans.

Based on the current operating plan, the Company believes that existing cash, cash equivalents and short-term investments, as of December 31, 2024 will enable the Company to fund operations into the fourth quarter of 2026 which includes scale up for the potential commercialization of RP1 in skin cancers and for working capital and general corporate purposes and excludes any potential revenue.
R&D Expenses: Research and development expenses were $48.0 million for the fiscal third quarter ended December 31, 2024, as compared to $42.8 million for the fiscal third quarter ended December 31, 2023. This increase was primarily due to an increase in personnel-related costs, as well as consulting and facility-related costs. Research and development expenses included $4.6 million in stock-based compensation expenses for the fiscal third quarter ended December 31, 2024.
S,G&A Expenses: Selling, general and administrative expenses were $18.0 million for the fiscal third quarter ended December 31, 2024, as compared to $13.7 million for the fiscal third quarter ended December 31, 2023. Selling, general and administrative expenses included $4.1 million in stock-based compensation expenses for the fiscal third quarter ended December 31, 2024.
Net Loss: Net loss was $66.3 million for the fiscal third quarter ended December 31, 2024, as compared to a net loss of $51.1 million for the fiscal third quarter ended December 31, 2023.
About RP1

RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

About RP2

RP2 is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity.

On February 12, 2025 HAYA Therapeutics, SA, a biotechnology company pioneering precision RNA-guided regulatory genome targeting therapeutics for rare, common, chronic and age-associated diseases, reported that it has been awarded the prestigious Innosuisse Certificate for Sustainable Growth from Innosuisse, the Swiss Innovation Agency, who also provided funding to support HAYA’s research into using its technology to address cancer (Press release, Haya Therapeutics, FEB 12, 2025, View Source [SID1234650229]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In addition to Innosuisse’s award for HAYA’s potential for growth and success, it is providing 1.5M CHF (approximately $1.64M USD) in non-dilutive funding for HAYA through Innosuisse’s Start-up Innovation Projects, recognizing HAYA’s cutting-edge approach and broad applicability of their long non-coding RNA (lncRNA) platform in developing disease-modifying therapeutics beyond the heart and into oncology.

The funds will be used over the next two years for translational studies to further develop an innovative therapy targeting cancer-associated fibroblast-specific lncRNA for aggressive solid tumors.

"Solid tumors, which make up approximately 90% of all cancers, require innovative therapeutic strategies due to their complexity and resistance to traditional treatments," said Samir Ounzain, Ph.D., Co-founder and CEO of HAYA Therapeutics. "Fibrosis plays a critical role in shaping the tumor microenvironment, creating a rigid and immunosuppressive barrier that fuels cancer progression and limits treatment efficacy. At HAYA, we are pioneering a novel RNA-guided approach to precisely reprogram cancer-associated fibroblasts, disrupting the fibrotic niche and unlocking new possibilities for more effective and durable cancer therapies."

"By leveraging the exquisite cell specificity of lncRNAs coupled with antisense oligonucleotide’s broad distribution to extra hepatic tissues including tumors, HAYA is able to drug disease modifying targets within the tumor microenvironment. This novel paradigm holds tremendous potential as a next generation treatment strategy for immunotherapy resistant solid tumors such as for pancreatic cancer and triple negative breast cancer," said Sudhir Agrawal, DPhil, FSRC, a member of HAYA’s scientific advisory board and Founder of Arnay Sciences. "HAYA’s strategy could be transformational and offer disease-modifying therapy options to patients in need."

HAYA’s unique RNA-guided regulatory genome technology enables the discovery and development of innovative RNA-based therapeutics for a wide range of diseases. HAYA’s lead candidate, HTX-001, is being developed for the treatment of heart failure, with other preclinical therapeutics in development for other indications.

On February 12, 2025 Rezolute, Inc. (Nasdaq: RZLT) ("Rezolute" or the "Company"), a late-stage biopharmaceutical company dedicated to developing transformative therapies for rare diseases with serious unmet needs, reported financial results and provided a business update for the three months ended December 31, 2024 (Press release, Rezolute, FEB 12, 2025, View Source [SID1234650212]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We have made significant regulatory progress with ersodetug and our focus in 2025 remains squarely on advancing both Phase 3 trials for patients with congenital HI and tumor HI," said Nevan Charles Elam, Chief Executive Officer and Founder of Rezolute. "We are encouraged by our momentum and remain dedicated to providing meaningful and innovative treatments for patients with limited options."

Recent Pipeline Progress and Anticipated Milestones

Congenital HI

· The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to ersodetug for the treatment of hypoglycemia due to congenital HI.
·
sunRIZE, a Phase 3, multicenter, double-blind, randomized, controlled safety and efficacy registrational study, is ongoing.

○ Enrollment of U.S. participants is anticipated to occur in the second quarter of 2025.
○ Overall study enrollment expected to conclude in the second quarter of 2025, with topline results expected in the fourth quarter of 2025, subject to outcomes from an interim analysis.

· An independent Data Monitoring Committee (DMC) reviewed safety and pharmacokinetics of ersodetug in eight infant participants in the open-label arm of the sunRIZE study.
○ Ersodetug administered between 5-10 mg/kg during a bi-weekly loading phase and a monthly maintenance phase was generally safe and well-tolerated.
○ Observed ersodetug drug levels at peak and trough were comparable to exposures in older pediatric participants in the Phase 2b RIZE study and validate the chosen dose regimen of 5 and 10 mg/kg administered bi-weekly and monthly.
○ Subsequent infant participants may be enrolled into the double-blind, placebo-controlled study.
○ The DMC did not analyze efficacy and the Company remains blinded to the results.

· An interim analysis of the primary study endpoint (change in hypoglycemia events) is planned for this quarter, with results and study update to be announced early in the second quarter.
○ Three possible outcomes from the analysis include: (i) futility and the study should be stopped, (ii) continue the study as is or (iii) continue the study as is but increase the sample size by 33% (18 additional patients) to enhance statistical confidence in the final outcome.

Tumor HI

· During the quarter, FDA granted Orphan Drug Designation to ersodetug for the treatment of hypoglycemia due to tumor HI.
· A Phase 3 registrational study for ersodetug in patients with tumor HI is anticipated to begin in the first half of 2025.
· Topline results are expected in the second half of 2026.

Fiscal Second Quarter Financial Results

Cash, cash equivalents and investments in marketable securities were $105.3 million as of December 31, 2024, compared to $127.1 million as of June 30, 2024.

Research and development expenses were $12.6 million for the second quarter of fiscal 2025, compared with $12.0 million for the same period a year ago, with the increase primarily attributable to increased expenditures in clinical trial activities, manufacturing costs and higher personnel-related expenses, which include employee compensation.

General and administrative expenses were $4.5 million for the second quarter of fiscal 2025, compared with $3.2 million for the same period a year ago, with the increase primarily attributable to professional fees and employee-related expenses as a result of increased headcount.

Net loss was $15.7 million for the second quarter of fiscal 2025 compared with a net loss of $13.9 million for the same period a year ago.

About Ersodetug

Ersodetug is a fully human monoclonal antibody that binds to a unique allosteric site on insulin receptors to counteract the effects of insulin receptor over-activation by insulin and related substances (such as IGF-2), thereby improving hypoglycemia in the setting of hyperinsulinism (HI). Because ersodetug acts downstream from the pancreas, it has the potential to be universally effective at treating hypoglycemia due to any form of HI.

About sunRIZE

The Phase 3 sunRIZE study is a multi-center, randomized, double-blind, placebo-controlled, parallel arm study designed to evaluate the efficacy and safety of ersodetug in patients with congenital HI who are experiencing poorly controlled hypoglycemia. Participants between the ages of 3 months to 45 years old are eligible to participate. The study is enrolling up to 56 participants in more than a dozen countries around the world.

On February 12, 2025 Terrain Biosciences reported the company launches from stealth as the world’s first RNA design-build company, using advanced AI and its proprietary manufacturing platform to accelerate development of the next generation of programmable medicines (Press release, Terrain Biosciences, FEB 12, 2025, View Source [SID1234650230]). RNA-based modalities, including mRNA, cell & gene therapies, and emerging personalized cancer vaccines are promising and rapidly advancing, with hundreds of drug candidates in development for indications ranging from oncology to infectious disease to neurodegenerative illnesses. Despite incredible progress, innovators in the space continue to face challenges in designing, selecting, manufacturing, and delivering optimal customized RNA sequences for therapeutic benefit.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Founded by Professors Omar Abudayyeh and Jonathan Gootenberg of Harvard Medical School and Professor Patrick Hsu of the Arc Institute and University of California, Berkeley, the company is led by industry veterans including CSO Aaron Larsen (formerly at Beam & Moderna), COO Ted Tisch (formerly at Mammoth Biosciences and Synthego), and founding CEO Chetan Tadvalkar (veteran GM/COO of pharma services companies, including former head of business operations at Ginkgo Bioworks). Terrain has raised $9M in seed funding to bring cutting-edge research in RNA design and manufacturing to innovators building RNA-based therapies and vaccines, and support development of personalized cancer vaccines. Over a dozen biotechs already trust Terrain Bio to help them identify and produce sequences with better expression, greater durability, and optimal manufacturability, accelerating their path to the clinic.

"AI is poised to dramatically accelerate how we design and develop drugs, but the reality is that in silico models can only get us so far in RNA — bringing a drug from the lab to the clinic requires bringing advanced science into the real world. Our partners need excellent machine learning tools combined with a real manufacturing platform and data to enable and accelerate their path to the clinic," said Terrain co-founder Omar Abudayyeh.

"Our partners are brilliant scientists on an incredibly challenging journey to develop new medicines and ultimately help patients," said Chetan Tadvalkar, CEO of Terrain. "Our team has been part of similar journeys before, and today our purpose is to help scientists navigate the complexity of designing the right RNA sequence and guide them towards their goal while ensuring they hit key preclinical milestones."

RNA optimization is critical for therapeutic efficacy and safety — sequence and purity reaches beyond the mechanism of action to have broad impacts across expression, stability, durability, immunogenicity, and manufacturability. "The search space for designing RNA is nearly infinite," said co-founder Jonathan Gootenberg. "Navigating that space computationally and experimentally will unlock enormous potential in medicine, but remains incredibly challenging given the lack of top-quality data for training better models."

"Bridging design and manufacturing in a tight feedback loop means higher quality preclinical data, which means stronger generative models for design, which means better drug candidates," said co-founder Patrick Hsu. "Terrain is all about making the tools for this kind of rapid iteration possible for delivering better RNA."

On February 12, 2025 MimiVax, Inc., a leader in clinical-stage pharmaceutical research, reported that its now fully enrolled Phase 2b clinical trial of SurVaxM in glioblastoma, [SURVIVE] (NCT05163080), has successfully progressed following the first interim analysis of trial data (Press release, MimiVax, FEB 12, 2025, View Source;utm_medium=rss&utm_campaign=mimivax-survaxm-interim-analysis [SID1234650255]). The analysis, conducted as part of the company’s rigorous clinical development program, has provided valuable insights that support the continued advancement of the trial. The purpose of this study is to determine whether adding SurVaxM to standard-of-care (resection, radiation/chemotherapy) is better than standard treatment alone for patients with newly diagnosed glioblastoma.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

While the company is unable to disclose specific details about the interim analysis due to regulatory requirements set forth by the U.S. Food and Drug Administration (FDA), MimiVax remains confident in the potential of SurVaxM and is committed to advancing the study as planned.

"We are encouraged by the progress of our clinical trial and remain focused on our goal to develop innovative therapies that can address glioblastoma and other cancers. Although we are unable to provide detailed information at this stage, we are excited about the continued advancement of this important program," said Dr. Michael Ciesielski, CEO of MimiVax. "We are working closely with the FDA to ensure compliance with regulatory guidelines as we move forward with the trial."

Based on the results of the recent interim futility analysis, and ongoing review by the study’s Independent Data Safety Monitoring Committee, the SURVIVE trial will continue as designed without modification.

The clinical trial is designed to evaluate the safety, efficacy, and overall benefit of SurVaxM in patients with newly diagnosed glioblastoma who receive standard-of-care treatment combined with SurVaxM at 11 participating major Cancer Centers in the United States. The company will provide updates at appropriate milestones, in accordance with regulatory requirements.

MimiVax thanks all participants, healthcare professionals, clinical support teams and investigators involved in the study for their continued support and commitment to the advancement of SurVaxM.

About SurVaxM:

SurVaxM is a peptide mimic immunogen that targets ‘survivin’, a cell-survival protein present in most glioblastomas and in many other cancers. SurVaxM stimulates a patients’ own immune response to control tumor growth and prevent disease recurrence. Because survivin is present in most cancers, SurVaxM could potentially have applicability in many other forms of cancer.