Oncotelic Therapeutics Highlights 2 Years of Clinical and Regulatory Advancements Across Late-Stage Pipeline

On September 12, 2025 Oncotelic Therapeutics, Inc. (OTCQB: OTLC) ("OTLC" or the "Company"), a clinical-stage biopharmaceutical company developing transformative oncology and immunotherapy treatments, reported a summary of its major accomplishments over the past two years (Press release, Oncotelic, SEP 12, 2025, View Source [SID1234655949]). These milestones underscore meaningful clinical progress and regulatory validation across the Company’s lead drug candidates.

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Oncotelic’s pipeline includes multiple late-stage programs targeting oncology and rare diseases, with several drug candidates achieving significant clinical milestones

Two-Year Clinical Progress Snapshot

OT-101 (TGF-β inhibitor): Phase 3 for pancreatic cancer, with additional applications in ARDS/COVID-19
OXi4503 (vascular disrupting agent): Phase 2 in AML/MDS; advancing toward pivotal phase 3 design
CA4P / Fosbretabulin: Late-stage oncology asset currently under repositioning
AL-101 (intranasal apomorphine): Phase 2 for Parkinson’s disease and sexual dysfunctions
AL-102 (oligonucleotide antisense via intrathecal injection): Discovery stage for Alzheimer’s disease
Pediatric Rare Disease Programs: Targeting orphan indications with the potential to generate Priority Review Vouchers (PRVs)
Nanomedicine Pipeline: Advancing multiple 505(b)(2) drug candidates into clinical testing, leveraging the 505(b)(2) pathway-a faster and more cost-efficient route to market approval compared to a full New Drug Application (NDA).
"OTLC has achieved steady progress across multiple programs, strengthening our position as a late-stage biotech with broad value creation potential. Our pipeline addresses multi-billion-dollar markets with high unmet medical need," said Dr. Vuong Trieu, Chairman and CEO of Oncotelic.

Indication Expansion Accelerates: First Patient Dosed in Melanoma Phase 1b/II Trial of Opamtistomig

On September 12, 2025 Nanjing Leads Biolabs Co., Ltd. ("Leads Biolabs" or the "Company," Stock Code: 9887.HK) reported the first patient has been successfully dosed in a Phase 1b/II clinical trial (NCT07099430) evaluating Opamtistomig (LBL-024, PD-L1/4-1BB bispecific antibody) as monotherapy or in combination with other agents for the ‌first-line treatment of advanced melanoma (Press release, Nanjing Leads Biolabs, SEP 12, 2025, View Source [SID1234655948])‌‌.

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Opamtistomig‌, a uniquely designed PD-L1/4-1BB bispecific antibody that simultaneously blocks PD-1/L1-mediated immune suppression and enhances 4-1BB-regulated T-cell activation. This dual mechanism has the potential to convert "cold tumors" into "hot tumors", overcoming resistance to immunotherapy and improving response rates in hard-to-treat cancers.

In two prior clinical trials, Opamtistomig demonstrated promising efficacy and a favorable safety profile in patients with highly malignant, immune-cold extrapulmonary neuroendocrine carcinoma (EP-NEC), both as monotherapy and in combination with chemotherapy. Notably, patient enrollment was completed in August 2025 for a pivotal single-arm registration trial evaluating Opamtistomig monotherapy in EP-NEC.

In addition, multiple Phase 1b/II studies are ongoing to assess Opamtistomig combined with chemotherapy for:

First-line small cell lung cancer (SCLC)‌
‌First-and second-line non-small cell lung cancer (NSCLC)
This newly initiated Phase 1b/II multicenter trial, led by Professor Chen Yu from Fujian Cancer Hospital, with participation from multiple hospitals, aims to evaluate Opamtistomig’s efficacy and safety in advanced melanoma as monotherapy or in combination regimens.

Dr. Charles Cai, Chief Medical Officer of Leads Biolabs, stated:

"The continued clinical advancement of Opamtistomig in EP-NEC and other tumor types highlights its unique ability to activate T cells while releasing immune suppression, offering hope to patients with immune-cold tumors who have limited treatment options. With more than 10 indications currently targeted across nine clinical trials, we are committed to accelerating development and delivering breakthrough therapies that expand the benefits of immunotherapy to more patients worldwide."

About Opamtistomig

Opamtistomig (LBL-024) is a potential first-in-class bispecific antibody simultaneously targeting PD-L1 and the co-stimulatory receptor 4-1BB. It is the first 4-1BB-targeting bispecific antibody globally to reach the single arm pivotal trial stage as a monotherapy and holds promise to become the first approved treatment specifically for extrapulmonary neuroendocrine carcinoma (EP-NEC), a malignancy with significant unmet medical need.

Developed using Leads Biolabs’ proprietary X-Body bispecific platform, Opamtistomig features a 2:2 format with two binding domains each for PD-L1 and 4-1BB, and an optimized affinity ratio. This design allows Opamtistomig to both reverse PD-L1–mediated immune suppression and selectively enhance T cell activation, resulting in potent, synergistic anti-tumor effects.

In two clinical trials in China, Opamtistomig has demonstrated promising efficacy and a favorable safety profile in patients with advanced EP-NEC, both as monotherapy and in combination with chemotherapy. The lack of a standard of care in EP-NEC supports the pursuit of accelerated approval through a single-arm pivotal study.

In recognition of its clinical potential, Opamtistomig received Breakthrough Therapy Designation (BTD) from the National Medical Products Administration (NMPA) in China (October 2024), and Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for neuroendocrine carcinoma (November 2024).

Notably, 4-1BB agonism can reactivate exhausted T cells and drive robust proliferation, making it particularly promising for PD-1/PD-L1-resistant or immunologically "cold" tumors. Beyond EP-NEC, Opamtistomig has been approved for clinical trials across multiple cancer types with high unmet need, including small cell lung cancer (SCLC), biliary tract cancer (BTC), ovarian cancer (OC), non-small cell lung cancer (NSCLC), esophageal squamous cell carcinoma (ESCC), hepatocellular carcinoma (HCC), gastric cancer (GC), triple-negative breast cancer (TNBC), and malignant melanoma. Encouraging clinical activity has already been observed in SCLC, BTC, OC, and other cancer types, supporting Opamtistomig’s potential as a broad-spectrum oncology therapy.

About Melanoma

Melanoma is a highly aggressive and life-threatening cutaneous malignancy, ranking as the third most common type of skin cancer. Although it represents only about 5% of all skin cancers, melanoma accounts for approximately 65% of skin cancer–related deaths.

Recent advances in immunotherapy—particularly PD-1/L1 and CTLA-4 inhibitors—have expanded treatment options and improved outcomes for many patients. However, melanoma epidemiology in China differs significantly from that of Western populations, with a predominance of acral and mucosal subtypes, which are considered "immunologically cold tumors."

Current immunotherapies, including PD-1/L1 and CTLA-4 inhibitors, show limited efficacy in these subtypes, with objective response rates (ORR) typically below 15%. Toripalimab, the only domestically developed PD-1 inhibitor approved as first-line therapy for Chinese melanoma patients, demonstrated an ORR of 11% and a median progression-free survival (PFS) of 2.3 months in registrational studies that primarily enrolled patients with acral and mucosal melanoma.

These data highlight a critical unmet medical need for more effective therapies for melanoma patients in China, particularly for those with acral and mucosal subtypes.

Interim results for the six months ended June 30, 2025

On September 12, 2025 Biodexa Pharmaceuticals PLC (Nasdaq: BDRX), a clinical stage biopharmaceutical company developing a pipeline of innovative products for the treatment of diseases with unmet medical needs, reported its unaudited interim results for the six months ended June 30, 2025 which will also be made available on the Company’s website at www.biodexapharma.com (Press release, Biodexa Pharmaceuticals, SEP 12, 2025, View Source [SID1234655947]).

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OPERATIONAL HIGHLIGHTS

The Company announced the following in the six months ended June 30, 2025:

· Allowance by the US Patent and Trademark Office of patent application No. 17/391-495 "Oral Rapamycin Nanoparticle Preparations and Use", exclusively licensed to the Company by Emtora Biosciences .

· Appointment of Precision for Medicine, LLC as the clinical research organization to conduct the European component of the upcoming registrational Phase 3 study of eRapa in FAP.

· A successful Type C meeting with the US Food and Drug Administration regarding the protocol for the Company’s registrational Phase 3 study of eRapa in FAP.

· Orphan Drug Designation granted for eRapa in FAP by the European Commission.

· Recruitment of the first patient in a Phase 2a study of tolimidone in Type 1 Diabetes in an Investigator Initiated Trial conducted by the University of Alberta Diabetes Institute.

· Selection of ‘Serenta’ as the brand name for its Phase 3 clinical study of eRapa in FAP together with launch of a dedicated website, www.serentatrial.com, to provide information and resources for patients, caregivers, and healthcare professionals.

· Activation of the first clinical study site in the US for its Serenta trial in patients with FAP.

Post period end:

· Filing of a Clinical Trial Application with the European Medicines Agency for its Serenta trial in patients with FAP.

· Enrolment of first patients in the Serenta trial by the Pan American Center for Oncology Trials in San Juan, Puerto Rico.

FINANCIAL HIGHLIGHTS

· Signing of a $35 million Equity Line of Credit with C/M Capital Master Fund LP, or C/M, pursuant to which the Company has the right, but not the obligation, to sell to C/M, and C/M is obligated to purchase newly issued ADSs for a period of 36 months.

· The Company’s collaboration partner, Emtora Biosciences, was awarded an additional grant of $3.0 million from the Cancer Prevention & Research Institute of Texas, bringing the total of non-dilutive grant funding to $20.0 million in support of the registrational Phase 3 program of eRapa in FAP.

· R&D costs decreased to £1.67 million in 1H25 (1H24: £2.19 million) reflecting a reduction in spend on the MAGIC-G1 study in recurrent glioblastoma and pre-clinical studies offset by an increase in expenditure (net of CPRIT grant income) on MTX230 (eRapa).

· Administrative costs increased to £2.38 million (1H24: £2.03 million) as a result of a foreign exchange charge offset by a reduction in transaction related costs.

· Net cash used in operating activities (after changes in working capital) in 1H25 was £3.30 million (1H24: £4.81 million).

· The Company’s cash balance at June 30, 2025 was £4.04 million.

Commenting, Stephen Stamp, CEO and CFO, said "The first half was extremely productive. Having secured Fast Track designation and successfully negotiated our way through a Type C meeting with the FDA, in August we enrolled the first patients into our pivotal Serenta trial of eRapa in FAP. In parallel, we secured orphan designation from the European Commission for eRapa in FAP in Europe and filed a Clinical Trial Application with the EMA, which sets us up to begin enrolment in the Serenta trial in Europe in the fourth quarter".

CHIEF EXECUTIVE’S REVIEW

Our main focus in the first half of 2025 was on preparatory activities for the start of our registrational Phase 3 trial of eRapa in Familial Adenomatous Polyposis ("FAP").

R&D update

In the first half of 2025 we materially advanced our R&D pipeline, moving eRapa in FAP into Phase 3 and tolimidone for Type 1 Diabetes ("T1D) into Phase 2:

eRapa

eRapa is a proprietary oral formulation of rapamycin, also known as sirolimus. Rapamycin is an mTOR (mammalian Target Of Rapamycin) inhibitor. mTOR has been shown to have a significant role in the signalling pathway that regulates cellular metabolism, growth and proliferation and is activated during tumorgenesis. Rapamycin is approved in the US for organ rejection in renal transplantation as Rapamune(Pfizer). Through the use of nanotechnology and pH sensitive polymers, eRapa is designed to address the poor bioavailability, variable pharmacokinetics and toxicity generally associated with the currently available forms of rapamycin. eRapa is protected by a number of issued patents which extend through 2035, with other pending applications potentially providing further protection beyond 2035.

Familial Adenomatous Polyposis ("FAP")

FAP is an orphan indication characterized by a proliferation of polyps in the colon and/or rectum, usually occurring in mid-teens. There is no approved therapeutic option for treating FAP patients, for whom active surveillance and surgical resection of the colon and/or rectum remain the standard of care. If untreated, FAP almost always leads to cancer of the colon and/or rectum. There is a significant hereditary component to FAP with a reported incidence of one in 5,000 to 10,000 in the US and one in 11,300 to 37,600 in Europe. eRapa has received Orphan Designation in the US and in Europe. Importantly, mTOR has been shown to be over-expressed in FAP polyps – thereby underscoring the rationale for using a potent and safe mTOR inhibitor like eRapa to treat FAP.

An open-label Phase 2 study (NCT04230499) was conducted by Emtora in seven U.S. centres of excellence in 30 adult patients. Patients were sequentially enrolled into three dosing cohorts of 10 patients each for a 12-month treatment period: 0.5mg every other day (Cohort 1), 0.5mg daily every other week (Cohort 2), and 0.5mg daily (Cohort 3). Upper and lower endoscopic surveillance occurred at baseline and after six months. Primary endpoints were safety and tolerability of eRapa and percentage change from baseline in polyp burden, as measured by the aggregate of all polyp diameters.

In May 2024 and June 2024, results of the Phase 2 study at six months and 12 months, respectively, were presented at prestigious scientific meetings by Carol Burke, MD, the Principal Investigator. In summary, at six months, eRapa appeared safe and well-tolerated with a significant 24% reduction in the total polyp burden at six months compared with baseline and an overall 83% non-progression rate. At 12 months, 21 of 28 (75%) patients were deemed to be non-progressors with a median reduction in polyp burden of 17%. In Cohort 2, the dosage regimen for Phase 3, eight of nine (89)% of patients were deemed non-progressors at 12 months with a median reduction in polyp burden of 29%. Over the course of 12 months, there were four related Grade 3 or higher and one related Serious Adverse Event reported during the trial and 95% compliance rate at 12 months. One patient was removed from the trial due to non-compliance.

The Phase 3 registrational study (NCT06950385) is a double-blind placebo-controlled design, recruiting 168 high risk patients diagnosed with germline or phenotypic FAP. The primary clinical endpoint is first progression free survival event which will comprise composite endpoints including major surgery. We had a successful ‘Type C’ meeting with the FDA in January 2025 to finalise the protocol. The first clinical site was initiated in June 2025 and the first patients enrolled by the Pan American Center for Oncology Trials in San Juan, Puerto Rico in August 2025. Europe is following closely behind; our contract research organisation, Precision for Medicine, was appointed in March 2025. Orphan Drug Designation for eRapa in FAP was granted by the European Commission in May 2025. A Clinical Trial Application was filed with the European Medicines Agency for the Serenta trial in July 2025 which, if approved, will facilitate the start of patient recruitment in Europe in 4Q25.

Non-muscle Invasive Bladder Cancer ("NMIBC")

NMIBC refers to tumors found in the tissue that lines the inner surface of the bladder. The most common treatment is transurethral resection of the bladder tumor followed by intravesical Bacillus Calmette-Guerin ("BCG") with chemotherapy depending upon assessment of risk of recurrence. NMIBC is the fourth most common cancer in men with an incidence of 10.1 per 100,000 and 2.5 per 100,000 in women.

The ongoing multi-centre, double-blind, placebo-controlled Phase 2 study in NMIBC (NCT04375813) is fully enrolled at 166 patients with primary endpoints of safety/tolerability and relapse free survival after 12 months of treatment. The study, which is supported by a $3.0 million non-dilutive grant from the National Cancer Institute, part of the National Institutes of Health, was transferred to the University of Texas, San Antonio as an Investigator Initiated Trial and is expected to read out in mid-2026.

MTD228 – Tolimidone

Tolimidone was originally discovered by Pfizer and was developed through Phase 2 for the treatment of gastric ulcers. Pfizer undertook a broad pre-clinical program to characterize the pharmacology, pharmacokinetics, metabolism and toxicology of tolimidone. Pfizer discontinued development of the drug due to lack of efficacy for that indication.

Tolimidone is a selective activator of the enzyme Lyn kinase which increases phosphorylation of insulin substrate-1, thereby amplifying the signalling cascade initiated by the binding of insulin to its receptor.

Type 1 Diabetes ("T1D")

Tolimidone’s potential utility in T1D has been demonstrated by several preclinical studies conducted by the University of Alberta, where Lyn kinase was identified as a key factor for beta cell survival and proliferation in in vitro and in vivo models. Most importantly, tolimidone appeared to induce proliferation in beta cells isolated from human cadavers. From a mechanism of action perspective, tolimidone has been shown to both prevent beta cell degradation and to stimulate beta cell proliferation. In a meta analysis of 1,202 articles and 193 studies, the incidence of T1D was shown to be 15 per 100,000 with a prevalence of 9.5 per 10,000 of the population.

As a first step in the continued clinical development of tolimidone, a Phase 2a Investigator Initiated Trial (IIT) at the University of Alberta Diabetes Institute (NCT06474598) is designed to establish the minimum effective dose of tolimidone in patients with T1D. The study, enrolled the first patient in June 2025 and is expected to recruit 12 patients initially across three dose groups. The study will measure C-peptide levels (a marker for insulin) and HbA1c (a marker for blood glucose) after three months compared with baseline and the number of hyperglycemic events.

MTX110

MTX110 is a solubilised formulation of the histone deacetylase (HDAC) inhibitor, panobinostat. This proprietary formulation enables delivery of the product via convection-enhanced delivery (CED) at chemotherapeutic doses directly to the site of the brain tumor, by-passing the blood-brain barrier and potentially avoiding systemic toxicity. All three types of brain cancer being studied are orphan.

Recurrent Glioblastoma ("rGBM")

Our Phase 1 MAGIC-G1 study (NCT05324501) of MTX110 in rGBM has completed the dose escalation part of the study with the recruitment of the fourth patient in Cohort A. Overall survival was reported as between 11 and 12 months. Glioblastoma virtually always recurs with median Progression Free Survival of 1.5–6.0 months and median Overall Survival of 2.0–9.0 months.

Diffuse Midline Glioma ("DMG")

In February 2024 we announced headline data from a Phase 1 IIT study conducted by Columbia University in newly diagnosed patients with DMG. As this was the first ever study of repeated infusions to the pons via an implanted CED catheter, the primary objective of the study was safety and tolerability and, accordingly, the number of infusions was limited to two, each of 48 hours, seven days apart in nine patients. One patient suffered a severe adverse event assessed by the investigators as not related to the study drug. Although not powered to reliably demonstrate efficacy, median Overall Survival of patients in the study was 16.5 months compared with median survival rate in a cohort of 316 cases of 10.0 months.

Study investigators subsequently presented the results of the trial at the 21st International Symposium on Pediatric Neuro-Oncology (ISPNO 2024) in Philadelphia, PA.

Medulloblastoma

An IIT Phase I study of MTX110 in medulloblastoma remains ongoing at the University of Texas.

Due to resource constraints, MTX110 has been de-prioritised and there are no current development activities being undertaken.

Financing

Equity Line of Credit

In January 2025, we entered into a securities purchase agreement, or equity line of credit ("ELOC"), with the newly formed C/M. Under the terms of the ELOC, we have the right, but not the obligation, to sell to C/M from time to time up to $35 million of newly issued ADSs over a 36-month period, unless the ELOC is terminated. As consideration for the execution and delivery of the ELOC, we agreed to pay a commitment fee ("Commitment Fee") of $875,000 in cash, of which (i) $612,500 was to be paid to C/M on signing the ELOC and (ii) the balance was to be paid pro rata, simultaneously with the delivery of any ADSs sold under the ELOC. We had the right to issue ADSs representing the value of the applicable portion of the Commitment Fee. We paid the initial Commitment Fee of $612,500 through the issuance of 140,080 Depositary Shares to the Purchaser.

We may direct C/M to purchase a specified number of ADSs not to exceed $2.5 million on any given day, at a price based on a formula, typically 95% of the closing price on the prior day. As of June 30, 2025, the Company had raised gross proceeds of $8.56 million from the ELOC.

Warrant Inducement

In May 2025 we entered into letter agreements with certain holders of outstanding Series E, Series H, Series J and Series K warrants to reduce the exercise price of such warrants to $0.31 per share. The holders exercised an aggregate of 200,433 warrants representing the same number of ADSs. We received gross proceeds of approximately $62,000, before offering expenses. The Company did not issue new warrants to replace the exercised warrants and did not engage a placement agent to facilitate the transaction.

Interim results for the six months ended June 30, 2025

On September 12, 2025 Biodexa Pharmaceuticals PLC (Nasdaq: BDRX), a clinical stage biopharmaceutical company developing a pipeline of innovative products for the treatment of diseases with unmet medical needs, reported its unaudited interim results for the six months ended June 30, 2025 which will also be made available on the Company’s website at www.biodexapharma.com (Press release, Biodexa Pharmaceuticals, SEP 12, 2025, View Source [SID1234655947]).

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!

OPERATIONAL HIGHLIGHTS

The Company announced the following in the six months ended June 30, 2025:

· Allowance by the US Patent and Trademark Office of patent application No. 17/391-495 "Oral Rapamycin Nanoparticle Preparations and Use", exclusively licensed to the Company by Emtora Biosciences .

· Appointment of Precision for Medicine, LLC as the clinical research organization to conduct the European component of the upcoming registrational Phase 3 study of eRapa in FAP.

· A successful Type C meeting with the US Food and Drug Administration regarding the protocol for the Company’s registrational Phase 3 study of eRapa in FAP.

· Orphan Drug Designation granted for eRapa in FAP by the European Commission.

· Recruitment of the first patient in a Phase 2a study of tolimidone in Type 1 Diabetes in an Investigator Initiated Trial conducted by the University of Alberta Diabetes Institute.

· Selection of ‘Serenta’ as the brand name for its Phase 3 clinical study of eRapa in FAP together with launch of a dedicated website, www.serentatrial.com, to provide information and resources for patients, caregivers, and healthcare professionals.

· Activation of the first clinical study site in the US for its Serenta trial in patients with FAP.

Post period end:

· Filing of a Clinical Trial Application with the European Medicines Agency for its Serenta trial in patients with FAP.

· Enrolment of first patients in the Serenta trial by the Pan American Center for Oncology Trials in San Juan, Puerto Rico.

FINANCIAL HIGHLIGHTS

· Signing of a $35 million Equity Line of Credit with C/M Capital Master Fund LP, or C/M, pursuant to which the Company has the right, but not the obligation, to sell to C/M, and C/M is obligated to purchase newly issued ADSs for a period of 36 months.

· The Company’s collaboration partner, Emtora Biosciences, was awarded an additional grant of $3.0 million from the Cancer Prevention & Research Institute of Texas, bringing the total of non-dilutive grant funding to $20.0 million in support of the registrational Phase 3 program of eRapa in FAP.

· R&D costs decreased to £1.67 million in 1H25 (1H24: £2.19 million) reflecting a reduction in spend on the MAGIC-G1 study in recurrent glioblastoma and pre-clinical studies offset by an increase in expenditure (net of CPRIT grant income) on MTX230 (eRapa).

· Administrative costs increased to £2.38 million (1H24: £2.03 million) as a result of a foreign exchange charge offset by a reduction in transaction related costs.

· Net cash used in operating activities (after changes in working capital) in 1H25 was £3.30 million (1H24: £4.81 million).

· The Company’s cash balance at June 30, 2025 was £4.04 million.

Commenting, Stephen Stamp, CEO and CFO, said "The first half was extremely productive. Having secured Fast Track designation and successfully negotiated our way through a Type C meeting with the FDA, in August we enrolled the first patients into our pivotal Serenta trial of eRapa in FAP. In parallel, we secured orphan designation from the European Commission for eRapa in FAP in Europe and filed a Clinical Trial Application with the EMA, which sets us up to begin enrolment in the Serenta trial in Europe in the fourth quarter".

CHIEF EXECUTIVE’S REVIEW

Our main focus in the first half of 2025 was on preparatory activities for the start of our registrational Phase 3 trial of eRapa in Familial Adenomatous Polyposis ("FAP").

R&D update

In the first half of 2025 we materially advanced our R&D pipeline, moving eRapa in FAP into Phase 3 and tolimidone for Type 1 Diabetes ("T1D) into Phase 2:

eRapa

eRapa is a proprietary oral formulation of rapamycin, also known as sirolimus. Rapamycin is an mTOR (mammalian Target Of Rapamycin) inhibitor. mTOR has been shown to have a significant role in the signalling pathway that regulates cellular metabolism, growth and proliferation and is activated during tumorgenesis. Rapamycin is approved in the US for organ rejection in renal transplantation as Rapamune(Pfizer). Through the use of nanotechnology and pH sensitive polymers, eRapa is designed to address the poor bioavailability, variable pharmacokinetics and toxicity generally associated with the currently available forms of rapamycin. eRapa is protected by a number of issued patents which extend through 2035, with other pending applications potentially providing further protection beyond 2035.

Familial Adenomatous Polyposis ("FAP")

FAP is an orphan indication characterized by a proliferation of polyps in the colon and/or rectum, usually occurring in mid-teens. There is no approved therapeutic option for treating FAP patients, for whom active surveillance and surgical resection of the colon and/or rectum remain the standard of care. If untreated, FAP almost always leads to cancer of the colon and/or rectum. There is a significant hereditary component to FAP with a reported incidence of one in 5,000 to 10,000 in the US and one in 11,300 to 37,600 in Europe. eRapa has received Orphan Designation in the US and in Europe. Importantly, mTOR has been shown to be over-expressed in FAP polyps – thereby underscoring the rationale for using a potent and safe mTOR inhibitor like eRapa to treat FAP.

An open-label Phase 2 study (NCT04230499) was conducted by Emtora in seven U.S. centres of excellence in 30 adult patients. Patients were sequentially enrolled into three dosing cohorts of 10 patients each for a 12-month treatment period: 0.5mg every other day (Cohort 1), 0.5mg daily every other week (Cohort 2), and 0.5mg daily (Cohort 3). Upper and lower endoscopic surveillance occurred at baseline and after six months. Primary endpoints were safety and tolerability of eRapa and percentage change from baseline in polyp burden, as measured by the aggregate of all polyp diameters.

In May 2024 and June 2024, results of the Phase 2 study at six months and 12 months, respectively, were presented at prestigious scientific meetings by Carol Burke, MD, the Principal Investigator. In summary, at six months, eRapa appeared safe and well-tolerated with a significant 24% reduction in the total polyp burden at six months compared with baseline and an overall 83% non-progression rate. At 12 months, 21 of 28 (75%) patients were deemed to be non-progressors with a median reduction in polyp burden of 17%. In Cohort 2, the dosage regimen for Phase 3, eight of nine (89)% of patients were deemed non-progressors at 12 months with a median reduction in polyp burden of 29%. Over the course of 12 months, there were four related Grade 3 or higher and one related Serious Adverse Event reported during the trial and 95% compliance rate at 12 months. One patient was removed from the trial due to non-compliance.

The Phase 3 registrational study (NCT06950385) is a double-blind placebo-controlled design, recruiting 168 high risk patients diagnosed with germline or phenotypic FAP. The primary clinical endpoint is first progression free survival event which will comprise composite endpoints including major surgery. We had a successful ‘Type C’ meeting with the FDA in January 2025 to finalise the protocol. The first clinical site was initiated in June 2025 and the first patients enrolled by the Pan American Center for Oncology Trials in San Juan, Puerto Rico in August 2025. Europe is following closely behind; our contract research organisation, Precision for Medicine, was appointed in March 2025. Orphan Drug Designation for eRapa in FAP was granted by the European Commission in May 2025. A Clinical Trial Application was filed with the European Medicines Agency for the Serenta trial in July 2025 which, if approved, will facilitate the start of patient recruitment in Europe in 4Q25.

Non-muscle Invasive Bladder Cancer ("NMIBC")

NMIBC refers to tumors found in the tissue that lines the inner surface of the bladder. The most common treatment is transurethral resection of the bladder tumor followed by intravesical Bacillus Calmette-Guerin ("BCG") with chemotherapy depending upon assessment of risk of recurrence. NMIBC is the fourth most common cancer in men with an incidence of 10.1 per 100,000 and 2.5 per 100,000 in women.

The ongoing multi-centre, double-blind, placebo-controlled Phase 2 study in NMIBC (NCT04375813) is fully enrolled at 166 patients with primary endpoints of safety/tolerability and relapse free survival after 12 months of treatment. The study, which is supported by a $3.0 million non-dilutive grant from the National Cancer Institute, part of the National Institutes of Health, was transferred to the University of Texas, San Antonio as an Investigator Initiated Trial and is expected to read out in mid-2026.

MTD228 – Tolimidone

Tolimidone was originally discovered by Pfizer and was developed through Phase 2 for the treatment of gastric ulcers. Pfizer undertook a broad pre-clinical program to characterize the pharmacology, pharmacokinetics, metabolism and toxicology of tolimidone. Pfizer discontinued development of the drug due to lack of efficacy for that indication.

Tolimidone is a selective activator of the enzyme Lyn kinase which increases phosphorylation of insulin substrate-1, thereby amplifying the signalling cascade initiated by the binding of insulin to its receptor.

Type 1 Diabetes ("T1D")

Tolimidone’s potential utility in T1D has been demonstrated by several preclinical studies conducted by the University of Alberta, where Lyn kinase was identified as a key factor for beta cell survival and proliferation in in vitro and in vivo models. Most importantly, tolimidone appeared to induce proliferation in beta cells isolated from human cadavers. From a mechanism of action perspective, tolimidone has been shown to both prevent beta cell degradation and to stimulate beta cell proliferation. In a meta analysis of 1,202 articles and 193 studies, the incidence of T1D was shown to be 15 per 100,000 with a prevalence of 9.5 per 10,000 of the population.

As a first step in the continued clinical development of tolimidone, a Phase 2a Investigator Initiated Trial (IIT) at the University of Alberta Diabetes Institute (NCT06474598) is designed to establish the minimum effective dose of tolimidone in patients with T1D. The study, enrolled the first patient in June 2025 and is expected to recruit 12 patients initially across three dose groups. The study will measure C-peptide levels (a marker for insulin) and HbA1c (a marker for blood glucose) after three months compared with baseline and the number of hyperglycemic events.

MTX110

MTX110 is a solubilised formulation of the histone deacetylase (HDAC) inhibitor, panobinostat. This proprietary formulation enables delivery of the product via convection-enhanced delivery (CED) at chemotherapeutic doses directly to the site of the brain tumor, by-passing the blood-brain barrier and potentially avoiding systemic toxicity. All three types of brain cancer being studied are orphan.

Recurrent Glioblastoma ("rGBM")

Our Phase 1 MAGIC-G1 study (NCT05324501) of MTX110 in rGBM has completed the dose escalation part of the study with the recruitment of the fourth patient in Cohort A. Overall survival was reported as between 11 and 12 months. Glioblastoma virtually always recurs with median Progression Free Survival of 1.5–6.0 months and median Overall Survival of 2.0–9.0 months.

Diffuse Midline Glioma ("DMG")

In February 2024 we announced headline data from a Phase 1 IIT study conducted by Columbia University in newly diagnosed patients with DMG. As this was the first ever study of repeated infusions to the pons via an implanted CED catheter, the primary objective of the study was safety and tolerability and, accordingly, the number of infusions was limited to two, each of 48 hours, seven days apart in nine patients. One patient suffered a severe adverse event assessed by the investigators as not related to the study drug. Although not powered to reliably demonstrate efficacy, median Overall Survival of patients in the study was 16.5 months compared with median survival rate in a cohort of 316 cases of 10.0 months.

Study investigators subsequently presented the results of the trial at the 21st International Symposium on Pediatric Neuro-Oncology (ISPNO 2024) in Philadelphia, PA.

Medulloblastoma

An IIT Phase I study of MTX110 in medulloblastoma remains ongoing at the University of Texas.

Due to resource constraints, MTX110 has been de-prioritised and there are no current development activities being undertaken.

Financing

Equity Line of Credit

In January 2025, we entered into a securities purchase agreement, or equity line of credit ("ELOC"), with the newly formed C/M. Under the terms of the ELOC, we have the right, but not the obligation, to sell to C/M from time to time up to $35 million of newly issued ADSs over a 36-month period, unless the ELOC is terminated. As consideration for the execution and delivery of the ELOC, we agreed to pay a commitment fee ("Commitment Fee") of $875,000 in cash, of which (i) $612,500 was to be paid to C/M on signing the ELOC and (ii) the balance was to be paid pro rata, simultaneously with the delivery of any ADSs sold under the ELOC. We had the right to issue ADSs representing the value of the applicable portion of the Commitment Fee. We paid the initial Commitment Fee of $612,500 through the issuance of 140,080 Depositary Shares to the Purchaser.

We may direct C/M to purchase a specified number of ADSs not to exceed $2.5 million on any given day, at a price based on a formula, typically 95% of the closing price on the prior day. As of June 30, 2025, the Company had raised gross proceeds of $8.56 million from the ELOC.

Warrant Inducement

In May 2025 we entered into letter agreements with certain holders of outstanding Series E, Series H, Series J and Series K warrants to reduce the exercise price of such warrants to $0.31 per share. The holders exercised an aggregate of 200,433 warrants representing the same number of ADSs. We received gross proceeds of approximately $62,000, before offering expenses. The Company did not issue new warrants to replace the exercised warrants and did not engage a placement agent to facilitate the transaction.

FORE Biotherapeutics Presents Phase 1/2a Plixorafenib Data Demonstrating Prolonged Duration of Effect in BRAF Altered Thyroid Cancers at American Thyroid Association® 2025 Annual Meeting

On September 12, 2025 FORE Biotherapeutics, a registration stage biotherapeutics company dedicated to developing targeted therapies to treat patients with cancer, reported new plixorafenib results from the previously completed Phase 1/2a clinical trial that demonstrate treatment with plixorafenib in patients with BRAF-altered papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) resulted in durable disease control that appears very favorable compared with historical data with standard treatment options (Press release, Fore Biotherapeutics, SEP 12, 2025, View Source [SID1234655946]). The data also demonstrate an encouraging safety profile consistent with previously reported results following treatment with plixorafenib. The data are being presented at the American Thyroid Association (ATA) 2025 Annual Meeting, taking place September 10-14, 2025 in Scottsdale.

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"These results presented at ATA 2025 demonstrate durable clinical benefit in both V600 mutated and BRAF fusion thyroid tumors, and durable disease control in patients with stable disease. These new findings continue to support the strong clinical profile of plixorafenib as well as the potential to benefit patients with BRAF-altered thyroid cancers," said Eric J. Sherman, M.D., Head and Neck Cancer Medical Oncologist at the Memorial Sloan Kettering Cancer Center, and Principal Investigator for the ongoing FORTE Phase 2 plixorafenib study. "Patients with differentiated thyroid cancer, including papillary thyroid cancers which account for about 80% of all thyroid cancers, are in dire need of new treatment options. BRAF V600E alterations occur in approximately 60% of papillary thyroid cancers, underscoring the need for development of a targeted therapy such as plixorafenib that addresses the mechanistic drivers of these tumors along with the compelling clinical efficacy and safety profile demonstrated by treatment with plixorafenib."

"We are excited to share these data that show additional evidence of strong and durable clinical activity of plixorafenib, in both BRAF V600 mutant and BRAF fusion thyroid cancers," said Stacie Peacock Shepherd, M.D., Ph.D., Chief Medical Officer of Fore. "The data also demonstrate a high duration of response in MAPKi-naïve patients, highlighting the unique mechanism of action of plixorafenib that avoids paradoxical MAPK pathway activation and delivers differentiated results as a single therapeutic agent in BRAF altered cancers. We continue to advance our ongoing registrational FORTE basket study, which includes BRAF V600 altered thyroid cancers, as we aim to generate further data to inform treatment and help patients with BRAF driven tumors."

The results presented at ATA 2025 are from 21 patients with thyroid cancer, 16 with PTC and 5 with ATC, treated with plixorafenib in a previously completed Phase 1/2a study that treated a total of 113 patients with advanced, unresectable solid tumors that were intolerant to standard therapy or had no standard therapy available. All 21 patients with thyroid cancer received prior radiation therapy, nearly all underwent prior surgery, and the majority had received prior systemic anticancer therapies. The safety profile of treatment with plixorafenib in patients with ATC or PTC was consistent with previously reported results from the Phase 1/2a study.

Treatment with plixorafenib with and without cobicistat in MAPK-inhibitor naïve patients with a BRAF V600 mutation demonstrated an encouraging clinical benefit with a differentiated duration of response and support plixorafenib’s paradox breaker mechanism of action in BRAF-altered tumors, including a median progression free survival (mPFS) of 63.9 months and a clinical benefit rate (CBR: response or stable disease ≥ 24 weeks) of 85.7% (6 of 7 patients). Four MAPK-inhibitor naïve PTC patients remained on treatment for over 5 years, including one partial response (PR) of 59.2 months (treatment duration=7.6 years) and a second PR of 30.9 months (treatment duration=8.3 years). In four ATC patients with a BRAF V600 mutation, all of whom were MAPK-inhibitor naïve, the mPFS was 16.1 months, with one confirmed PR lasting 17.8 months and two patients reaching stable disease. In the three PTC patients that received prior MAPK inhibition therapy as well as at least one prior BRAF inhibition therapy, all three patients reached stable disease, with a CBR of 33.3%. Clinical benefit was also observed in patients with BRAF fusion PTC, with one of three patients achieving a PR lasting 12.9 months (treatment duration=25 months, continued post-study completion), and one patient with ATC having stable disease.

The results presented at ATA 2025 demonstrate a differentiated and durable clinical benefit in BRAF altered anaplastic and papillary thyroid cancers, compared to historical results of approved and investigational therapies, including BRAF, MEK, and pan-RAF inhibitors. Plixorafenib’s novel mechanism of action does not induce paradoxical activation of the MAPK pathway, thereby not requiring combination with a MEK inhibitor and potentially improving upon safety, efficacy, and durability compared with treatments containing prior generation RAF inhibitors.

FORE is advancing the registration-intended FORTE Master Protocol, a global Phase 2 clinical trial which includes four sub-protocol baskets evaluating plixorafenib in distinct patient populations. The three monotherapy indications currently under evaluation are BRAF V600 progressive or recurrent primary CNS tumors, rare BRAF V600 mutated advanced solid tumors, including ATC, and solid tumors with BRAF fusions, including PTC and ATC. BRAF v600E alterations occur in 45% of ATC and approximately 60% of PTC, representing a differentiated potential future development opportunity for plixorafenib.

Poster Presentation Details:

Title: Clinical Activity and Safety of Novel BRAF Inhibitor (BRAFi) Plixorafenib (FORE8394; PLX8394) in Advanced Thyroid Cancers (TC) Harboring BRAF Alterations
Lead Author & Presenter: Eric J. Sherman, M.D., Memorial Sloan Kettering Cancer Center
Poster Session: Clinical Thyroid Diseases & Cancer
Date and Time: Friday, September 12, 2025, 3:00 – 4:00 p.m. MT
Poster Number: 300