On September 19, 2024 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, reported positive clinical results from BRACELET-1, its randomized Phase 2 study evaluating pelareorep in patients with HR+/HER2- advanced or metastatic breast cancer (Press release, Oncolytics Biotech, SEP 19, 2024, View Source [SID1234646747]).

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Final BRACELET-1 Results

Final BRACELET-1 efficacy data were collected and analyzed two years after the last patient was enrolled as specified by the protocol. Results of the final BRACELET-1 analysis show that the median OS was not reached in the pelareorep + paclitaxel arm, as more than half of the patients in that arm remained alive at study end. In contrast, median OS for the paclitaxel monotherapy arm was 18.2 months, and the hazard ratio was 0.48 for pelareorep + paclitaxel vs. the paclitaxel monotherapy. Had study follow-up continued beyond two years, and patients survived only until the next planned visit (in four months), the median OS for patients in the pelareorep + paclitaxel arm would be 32.1 months. In accordance with these results, the two-year survival rate for patients in the pelareorep + paclitaxel arm was 64% compared to 33% for paclitaxel monotherapy patients. Additionally, the final median progression-free survival (PFS) for BRACELET-1 was 12.1 months in the pelareorep + paclitaxel arm vs. 6.4 months in the paclitaxel monotherapy arm, representing a 5.7-month benefit with a hazard ratio of 0.39.

Confirmed overall response rate (ORR) was 37.5% for pelareorep + paclitaxel and 13.3% for paclitaxel. As previously reported, ORRs at week 16 (the trial’s primary endpoint) in the pelareorep + paclitaxel and paclitaxel monotherapy cohorts were 31% and 20%, respectively.

"The fact that the median overall survival was not reached because more than half the patients were still alive at the end of the study is a remarkable achievement for us," said Wayne Pisano, Interim CEO and Chair of Oncolytics’ Board of Directors. "It shows just how promising pelareorep treatment can be for extending the lives of breast cancer patients. This is further exemplified by the near doubling of the 2-year survival rate for patients who received pelareorep combination therapy."

Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics, commented, "The overall survival and final progression-free survival results from the BRACELET-1 final analysis exceeded our expectations. In addition, our translational data strongly suggest that the OS benefit was linked to pelareorep’s immunologic activity. Taken together, the BRACELET-1 results provide compelling support for the potential of pelareorep-based combination therapy to benefit patients with advanced or metastatic HR+/HER2- breast cancer. Moreover, these results substantiate the statistically significant near doubling of median overall survival observed in the earlier randomized IND-213 study in a similar patient population treated with pelareorep + chemotherapy compared to chemotherapy alone. Having recently discussed with the FDA key design elements for our next breast cancer study, in combination with the strong survival data from the BRACELET-1 and IND-213 studies, we are confident in our plan to conduct a registration-enabling study to assess pelareorep-based combination therapy in patients with advanced HR+/HER2- breast cancer."

Professor Martine J. Piccart, M.D., Ph.D. Université Libre de Bruxelles commented, "While there has been progress in the treatment of advanced and metastatic breast cancer, an unmet medical need remains. With the encouraging results of BRACELET-1 and the prior positive results of the IND-213 study, pelareorep should continue to be developed and evaluated in the clinical setting."

Final BRACELET-1 Results:

Paclitaxel (PTX) Monotherapy (n=15) PTX + Pelareorep (n=16)
PTX + Pelareorep + Avelumab (n=17) 2
Confirmed ORR Over Course of Trial 2 (13.3%) 6 (37.5%) 3 (17.6%)
Median PFS (months)
6.4
(95% CI: 3.7, NR)
12.1
(95% CI: 6.6, 15.9)
6.4
(95% CI: 4.0, 7.5)
PFS Hazard Ratio vs. PTX Monotherapy -
0.39
(95% CI: 0.12, 1.24)
1.43
(95% CI: 0.49, 4.12)
Median OS (months) 18.2 Not Reached 21.7
Estimate: 32.11
OS Hazard Ratio vs. PTX Monotherapy -
0.48
(95% CI: 0.17, 1.35)
1.08
(95% CI: 0.45, 2.57)
24-month OS Rate 33% 64% 39%
Notes:
1This estimate assumes patients survived only until the next per protocol follow-up in 4 months. Had the patients survived only one day past their final follow-up visits, the estimated median OS would be 28.7 months.
2The positive clinical effects observed in the pelareorep + paclitaxel arm were not observed in the study group that received avelumab. The activation of cytotoxic T cells by pelareorep, critical for its anti-tumor effect, was suppressed by the addition of avelumab. This likely resulted from avelumab’s ability to bind Fc receptors, leading to the elimination of pelareorep-induced immune responses through antibody-dependent cellular cytotoxicity and other mechanisms.
3The three BRACELET-1 study groups were well balanced for key attributes that could affect response to therapy, including performance status, presence of visceral disease, and post-progression therapy.

Christophe Degois, VP of Business Development for Oncolytics commented, "With the evolving breast cancer treatment paradigm and the introduction of antibody-drug conjugate therapies, pelareorep has the potential to provide an important alternative for patients considering chemotherapy as their next treatment option. Upon thorough analysis of the HR+/HER2- metastatic breast treatment cancer landscape, we believe that pelareorep could have a substantial impact on around 55,000 patients in the US, representing a significant commercial opportunity."

About BRACELET-1
The BRACELET-1 (BReast cAnCEr with the Oncolytic Reovirus PeLareorEp in CombinaTion with anti-PD-L1 and Paclitaxel) study is an open-label, phase 2, randomized study in patients with HR+/HER2-, endocrine-refractory metastatic breast cancer. The study randomized 45 patients 1:1:1 into three cohorts. A three-patient safety run-in was also conducted with patients receiving pelareorep, paclitaxel, and avelumab prior to randomization. The three cohorts are treated as follows:

•Cohort 1: paclitaxel

•Cohort 2: paclitaxel + pelareorep

•Cohort 3: paclitaxel + pelareorep + avelumab (Bavencio)

Patients in cohort 1 receive paclitaxel on days 1, 8, and 15 of a 28-day cycle. Patients in cohort 2 receive the same paclitaxel regimen as cohort 1, plus pelareorep on days 1, 2, 8, 9, 15 and 16 of the 28-day cycle. Patients in cohort 3 receive the same combination and dosing regimen as cohort 2, plus avelumab on days 3 and 17 of the 28-day cycle. The primary endpoint of the study is overall response rate at week 16. Exploratory endpoints include progression-free survival, peripheral and tumor T cell clonality, inflammatory markers, and safety and tolerability assessments.

On September 19, 2024 MEI Pharma, Inc. (Nasdaq: MEIP) (the "Company") reported results for its fiscal year ended June 30, 2024 (Press release, MEI Pharma, SEP 19, 2024, View Source [SID1234646749]).

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Previously on July 22, 2024, the Company announced the commencement of an evaluation of strategic alternatives with the goal of maximizing the value of its assets for its stockholders. Subsequent to that date, the Company announced the engagement of Oppenheimer & Co., Inc. to serve as the Company’s exclusive financial adviser to assist in the review and evaluation of that process. As part of the review of strategic alternatives, the Company will consider options such as out-licensing opportunities for existing programs and merger and acquisition opportunities.

To best preserve the Company’s existing cash, the Company commenced a reduction-in-force on August 1, 2024, which will continue in stages as the Company’s operational and strategic direction evolves. Additionally, while the Company has discontinued the clinical development of voruciclib, certain non-clinical activities related to the Company’s drug candidates continue to be conducted.

There can be no assurance the exploration of strategic alternatives will result in any agreements or transactions, or, if completed, any agreements or transactions will be successful or on attractive terms. The Company does not expect to disclose developments with respect to this process unless or until the evaluation of strategic alternatives has been completed or the Board of Directors has concluded disclosure is appropriate or legally required.

As of June 30, 2024, MEI had $38.3 million in cash, cash equivalents, and short-term investments with no outstanding debt.

On September 19, 2024 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 fourth quarter and full fiscal year ended June 30, 2024 (Press release, Rezolute, SEP 19, 2024, View Source [SID1234646750]).

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"We are thrilled to close out the year with FDA alignment to advance ersodetug in two Phase 3 rare disease programs for the treatment of hypoglycemia resulting from congenital and acquired forms of hyperinsulinism," said Nevan Elam, Chief Executive Officer and Founder of Rezolute. "The Phase 3 sunRIZE study remains on track for ex-U.S. participant enrollment and we expect U.S. enrollment to begin in the first part of 2025. We look forward to progressing both Phase 3 studies and remain excited at the prospect of ersodetug as a best-in-class treatment for hyperinsulinism based on the success we’ve seen to date."

Recent Pipeline Progress and Anticipated Milestones

Congenital HI

U.S. Food and Drug Administration (FDA) removal of partial clinical holds on ersodetug, a potential treatment for hypoglycemia caused by congenital HI, and authorization of U.S. inclusion in the ongoing Phase 3 sunRIZE study.
Commencing study start-up activities in the U.S. with the goal of including U.S. participants in early 2025.
Ex-U.S. patient enrollment in sunRIZE is on track.
Topline results from sunRIZE expected in the second half of 2025.
Tumor HI

FDA clearance of Investigational New Drug (IND) application for Phase 3 registrational study for ersodetug for the treatment of hypoglycemia caused by tumor HI.
Start-up activities are ongoing for the study, which will be primarily conducted in the U.S., with patient enrollment anticipated to begin in the first half of 2025.
Topline results expected in the second half of 2026.
Several insulinoma patients have been treated with ersodetug in the Expanded Access Program (EAP).
Diabetic Macular Edema (DME)

Announced positive topline results in May of 2024 from the Phase 2 proof-of-concept study of RZ402 in patients with DME.
The study met primary endpoints, demonstrating good safety and tolerability, and a significant reduction in central subfield thickness (CST) in the Study Eye at all RZ402 dose levels compared to placebo (up to approximately 50 micron improvement).
We are actively engaged in conversations with potential partners to take RZ402 into further development.
Fourth Quarter and Full Year Fiscal 2024 Financial Results

Cash, cash equivalents and investments in marketable securities were $127.1 million as of June 30, 2024, compared with $118.4 million as of June 30, 2023.

Research and development (R&D) expenses were $19.1 million for the fourth quarter of fiscal 2024, compared with $10.9 million for the same period a year ago. Full fiscal year 2024 R&D expenses were $55.7 million, compared to $43.8 million in fiscal year 2023. The increase from fiscal year 2023 to fiscal year 2024 was primarily due to (i) increased expenditures in clinical trial activities, (ii) manufacturing costs for ersodetug, (iii) milestone payments due to license agreement partners, and (iv) higher employee-related expenses, which included employee compensation and stock-based compensation.

General and administrative (G&A) expenses were $4.0 million for the fourth quarter of fiscal 2024, compared with $3.3 million for the same period a year ago. Full fiscal year 2023 G&A expenses were $14.7 million, compared to $12.2 million in fiscal year 2023. The increase was primarily attributable to employee-related expenses due to increased headcount and professional fees.

Net loss was $23.0 million for the fourth quarter of fiscal 2024 compared with a net loss of $12.7 million for the same period a year ago. Full year fiscal 2024 net loss was $68.5 million compared to net loss of $51.8 million for the fiscal year 2023.

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 September 19, 2024 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), reported that the United States Food and Drug Administration (FDA) has granted Fast Track Designation to Amplia’s Focal Adhesion Kinase inhibitor, narmafotinib, for the treatment of advanced pancreatic cancer (Press release, Amplia Therapeutics, SEP 19, 2024, View Source [SID1234646751]).

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Fast Track Designation is available to drugs that may provide an advantage over current therapies in the treatment of serious conditions. It is designed to speed the development of these drugs to enable patients to receive them sooner. This Designation will grant the Company access to more frequent meetings, and written communication, with the FDA. In future, narmafotinib may be eligible for Accelerated Approval and Priority Review. The Company has previously received Orphan Drug Designation from the FDA for narmafotinib in pancreatic cancer.

The Company’s CEO and Managing Director, Dr Chris Burns, commented, "Fast Track Designation for narmafotinib is a significant milestone for the Company. With this designation, we can work more closely with the FDA to accelerate our clinical program and gather the most compelling evidence for regulatory approval in this devastating disease."

Amplia’s clinical trial in advanced pancreatic cancer, the ACCENT trial, is ongoing in Australia and South Korea. Earlier this year, the Company announced that the US FDA had cleared its IND1 application for a trial of narmafotinib in pancreatic cancer in the US. This trial is in advanced planning stages.

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics.

About Narmafotinib

Narmafotinib (AMP945) is the company’s best-in-class inhibitor of the protein FAK, a protein overexpressed in pancreatic and other cancers, and a drug target gaining increasing attention for its role in solid tumours. The drug, which is a highly potent and selective inhibitor of FAK, has shown promising data in a range of preclinical cancer studies. The drug has successfully completed a healthy volunteer study and is currently in an open-label Phase 2a trial in pancreatic cancer where a combination of narmafotinib and the chemotherapies gemcitabine and Abraxane is being assessed for safety, tolerability and efficacy.

On September 18, 2024 Ascendis Pharma A/S (Nasdaq: ASND) reported that it has commenced an underwritten public offering of $300,000,000 of American Depositary Shares ("ADSs"), each of which represents one ordinary share of Ascendis (Press release, Ascendis Pharma, SEP 18, 2024, View Source [SID1234646718]). All of the ADSs are being offered by Ascendis. In addition, Ascendis expects to grant the underwriters a 30-day option to purchase up to an additional $45,000,000 of ADSs at the public offering price, less the underwriting commissions. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the proposed offering.

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J.P. Morgan, Morgan Stanley, Evercore ISI and Goldman Sachs & Co. LLC are acting as joint book-running managers for the proposed offering.

A shelf registration statement relating to these securities was filed with the U.S. Securities and Exchange Commission ("SEC") on September 18, 2024, and automatically became effective upon filing. This proposed offering is being made solely by means of a prospectus. A copy of the preliminary prospectus supplement and the accompanying prospectus relating to this proposed offering, when available, may be obtained by contacting J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by email at [email protected]; Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014, or by email at [email protected]; Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 35th Floor, New York, NY 10055, or by telephone at (888) 474-0200, or by email at [email protected]; or Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at (866) 471-2526, or by email at [email protected]..

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.