On October 23, 2024 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, reported that preliminary safety results on its WEE1 inhibitor APR-1051 are highlighted in a poster being presented today at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics, taking place in Barcelona, Spain (Press release, Aprea, OCT 23, 2024, View Source [SID1234647329]).

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The results are from ACESOT-1051, a first-in-human Phase 1 study assessing the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations.

The dose escalation part of the study (Part 1) is currently ongoing and is expected to include up to 39 patients with advanced solid tumors. Oral APR-1051 is being administered once daily for 28-day cycles. A total of 8 cohorts are planned, evaluating doses of 10 mg to 150 mg once daily. So far, patients have been enrolled in single patient Cohorts 1, 2 and 3, evaluating subtherapeutic doses of 10 mg, 20 mg and 30 mg, respectively.

Preliminary results

Data are available on two of three patients, with a cutoff date of October 7, 2024

Preliminary results demonstrate that APR-1051 is safe and well-tolerated with no hematologic toxicity
Hemoglobin, hematocrit, and platelet counts were stable or increased slightly during the first treatment cycle
There were no signs of neutropenia, with white blood cells and neutrophils trending up for both patients during the first treatment cycle
All adverse events (AEs) recorded were Grade 1 and 2, with one Grade 1 AE (abdominal distention) possibly related to APR-1051
No QT prolongation has been observed
Three patients have been dosed to date with data available on two of these. One had disease progression at 49 days, a second withdrew following 36 days of treatment and dosing is ongoing in the third patient.
"These preliminary data from our ongoing Phase 1 study are encouraging, showing that APR-1051 is safe and well-tolerated," said Philippe Pultar, MD, Senior Medical Advisor and Lead of WEE1 Clinical Development at Aprea. "APR-1051 has been designed to be selective for WEE1, without the off-target inhibition of PLK or QT prolongation reported for other molecules in this class. We expect to confirm this favorable safety profile as we move to higher doses in the ACESOT-1051 trial. We are excited to explore the full therapeutic benefits of APR-1051, which has best in class potential, and hope to generate preliminary efficacy data from the study during 2025."

APR-1051 targets WEE1 kinase, an enzyme involved in the DNA damage response pathway. Based on preclinical studies, Aprea believes that APR-1051 may solve liabilities associated with other WEE1 inhibitors and is differentiated based on: 1) molecular structure; 2) selectivity for WEE1 versus off-target inhibition of the polo-like kinase, or PLK, family of kinases; 3) potentially improved pharmacokinetic (PK) properties; and 4) potential absence of QT prolongation at doses that significantly inhibit WEE1. No head-to-head studies with APR-1051 have been conducted.

Active enrollment in ACESOT-1051 is ongoing at three sites in the U.S. (NEXT Oncology locations in San Antonio and Dallas, and The University of Texas MD Anderson Cancer Center) with planned additional sites.

Anthony Tolcher M.D., Founder of Next Oncology commented, "The preliminary findings from ACESOT-1051 are promising and we are encouraged by the minimal toxicity in the patients treated so far. WEE1 kinase is a validated oncology target and represents an opportunity for therapeutic intervention in patients who otherwise have poor prognosis and no effective treatments today. We look forward to further exploring APR-1051’s potential and are excited to recruit additional patients as the study progresses."

ACESOT-1051 Study Design

ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) is a focused biomarker-driven study designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. Oral APR-1051 will be administered once daily for 28-day cycles. The study consists of two parts: Part 1 is dose escalation and is expected to enroll up to 39 patients with advanced solid tumors. The first three dose levels are using accelerated titration followed by Bayesian Optimal Interval (BOIN) design for the remaining dose levels; Part 2 (up to 40 patients) is designed for dose optimization, with the goal of selecting the Recommended Phase 2 Dose (RP2D). For more information, refer to Clinicaltrials.gov: NCT06260514.

A copy of the poster will be available on Aprea’s corporate website today. Three additional posters will be available at the conclusion of the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Friday, October 25, 2024.

On October 23, 2024 Alpha-9 Oncology Inc. (Alpha-9 or the Company), a clinical stage company developing radiopharmaceuticals to meaningfully improve the treatment of people living with cancer, reported an oversubscribed $175 million Series C financing to support the progression of its pipeline (Press release, Alpha9 Oncology, OCT 23, 2024, View Source [SID1234647328]). The financing was led by Lightspeed Venture Partners and Ascenta Capital. A selected syndicate of new investors – General Catalyst, a16z Bio + Health, RA Capital Management, Janus Henderson Investors, Delos Capital, Digitalis Ventures, Lumira Ventures and a healthcare fund managed by abrdn Inc. – joined the round, in addition to existing investors Frazier Life Sciences, Longitude Capital, Nextech Invest, BVF Partners LP, and Samsara BioCapital. Shelley Chu, head of Lightspeed Venture Partners’ healthcare team and Evan Rachlin, co-founder and managing partner of Ascenta Capital will join the Company’s Board of Directors.

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Alpha-9 has built a diversified portfolio of clinical and discovery assets across both validated and novel targets. The Series C will fund human studies for the clinical stage assets and advancement of discovery stage assets to clinic-ready development candidates. Furthermore, the Series C will fund expanded R&D capabilities and continued investment in CMC and supply chain.

"Over the last few years, Alpha-9 has built a leading radiopharmaceutical company with a deep pipeline and robust infrastructure," said Alpha-9 CEO, David Hirsch, MD, PhD. "The Series C is an exciting, significant milestone for us and will greatly accelerate our growth. We are thrilled to have the backing of a top-tier investor syndicate who share our belief in the potential of radiopharmaceuticals."

"Alpha-9 is developing a differentiated portfolio that includes multiple radiopharmaceuticals with first in-class and best-in-class potential," said Shelley Chu, head of Lightspeed Venture Partners’ healthcare team. "We are impressed with the team’s progress to date and are proud to support the advancement of these programs."

Alpha-9’s approach to designing bespoke molecules is systematic and data-driven. The Company has a differentiated toolbox of binders, linkers, chelators and radioisotopes – elements that each play an integral role in radiopharmaceutical development. Alpha-9 designs each component of the radiopharmaceutical for optimal selectivity, stability and payload delivery. The Alpha-9 approach is rigorous, fast and capital efficient, generating best-in-class compounds for rapid clinical development.

"We have been following this space for a long time. What differentiated Alpha-9 was its effective approach to molecule design as well as its thoughtful strategy on infrastructure expansion," said Evan Rachlin, MD, managing partner of Ascenta Capital. "We are pleased to support the Company’s continued progress as it strives to deliver on the promise of radiopharmaceuticals."

To support its endeavors, Alpha-9 has purpose-built research facilities in Vancouver, which were completed last year and have been operating at scale. These facilities help to accelerate drug development by streamlining discovery processes. Alpha-9 has also partnered with isotope suppliers and CDMOs to support its ongoing clinical trials. Alpha-9’s commitment to continue building robust infrastructure and world class capabilities underscores the company’s mission to provide effective treatments for patients worldwide.

On October 22, 2024 (the "Closing Date"), MEI Pharma, Inc., a Delaware corporation (the "Company"), and Aardvark Therapeutics, Inc., a Delaware corporation (the "Purchaser"), reported to have entered into an Asset Purchase Agreement (the "Asset Purchase Agreement"), pursuant to which the Company sold its rights, title and interest in and to certain assets related to ME-344 (the "Program Candidate"), including relevant intellectual property rights, technology and contracts (Filing, 8-K, MEI Pharma, OCT 22, 2024, View Source [SID1234647440]). Pursuant to the Asset Purchase Agreement, the Purchaser paid the Company an initial payment of $500,000 in cash plus the Reimbursement Amount (as defined in the Asset Purchase Agreement) at the closing of the transactions contemplated by the Asset Purchase Agreement (the "Closing") and may make payments up to $62 million after the Closing (the "Milestone Payments"), payable upon the achievement of certain milestones regulatory approval and sales related to the Program Candidate (the "Milestone Events"). The Purchaser also assumed certain liabilities of the Company arising after the Closing, including liabilities arising under the transferred contracts.

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The Asset Purchase Agreement and the transactions contemplated therein were approved by the board of directors of the Company. The Asset Purchase Agreement contains customary representations, warranties and covenants of each of the Company and the Purchaser. Subject to specified survival limitations, the representations and warranties contained in the Asset Purchase Agreement terminated immediately following the Closing.

Other than the Asset Purchase Agreement, there exists no material relationship between the Company, its affiliates or any of the Company’s directors and officers, on the one hand, and the Purchaser, on the other. The terms of the transaction were negotiated between the Company and the Purchaser on an arms-length basis.

The foregoing description of the Asset Purchase Agreement is qualified in its entirety by reference to the complete text of the Asset Purchase Agreement, which is attached as Exhibit 2.1 to this Current Report on Form 8-K and incorporated herein by reference.

The Asset Purchase Agreement contains representations and warranties that the parties made to, and are solely for the benefit of, each other. Investors and security holders should not rely on the representations and warranties as characterizations of the actual state of facts since they were made only as of the date of the Asset Purchase Agreement. Moreover, information concerning the subject matter of such representations and warranties might change after the date of the Asset Purchase Agreement, which subsequent information might or might not be fully reflected in public disclosures.

On October 22, 2024, vTv Therapeutics LLC ("vTv LLC"), a controlled subsidiary of vTv Therapeutics Inc. (the "Company"), reported to have received notice from OnKure Therapeutics, formerly Reneo Pharmaceuticals, Inc. ("OnKure"), of their intent to terminate the License Agreement between vTv LLC and Reneo Pharmaceuticals, Inc., dated December 21, 2017, as amended December 20, 2021 (the "Agreement") (Filing, 8-K, vTv Therapeutics, OCT 22, 2024, View Source [SID1234647426]). Under the Agreement, the Company had granted OnKure an exclusive, worldwide license to intellectual property pertaining to the Company’s peroxisome proliferator-activated receptor delta (ppar-δ) agonist program. In its notice, OnKure indicated that it had decided to discontinue development of the program. Under the Agreement, the termination will become effective as of January 20, 2025.

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On October 22, 2024 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) ("BriaCell" or the "Company"), a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care, reported new positive survival data, outperforming patients, and survival rates in its Phase 2 metastatic breast cancer (MBC) study (Press release, BriaCell Therapeutics, OCT 22, 2024, View Source [SID1234647332]).

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In BriaCell’s Phase 2 clinical study, patients treated with the same Bria-IMT regimen formulation being used in the ongoing Phase 3 pivotal trial experienced a one-year survival rate of 55% (i.e. 55% of patients remain alive at least one year after starting on the study). This rate exceeds the survival data of the current standard of care for similar patients (see Table 1). Notably, 4 of 13 patients recruited in 2022 remain in survival follow-up as well, including:

Patient 01-009: Overall survival (OS) of 25 months has been reported in a patient who had failed 6 prior treatments prior to the BriaCell regimen. Stable disease and lymph node shrinkage has been recorded during 13 cycles of therapy.
Patient 07-001: OS of 24 months. She had stable disease and received 8 cycles of BriaCell’s therapy.
Patient 16-003: OS of 15 months and received 8 cycles of therapy with stable disease. Prior to the BriaCell regimen, she had 7 lines of therapy, which included the progression of disease while on the antibody-drug conjugate (ADC) Enhertu.
Patient 11-018: OS of 14 months. This previously-reported responder with 100% resolution of her brain metastasis has recently completed her 19th cycle of therapy.
"With over 40,000 deaths each year in the US alone, late-stage MBC remains an important unmet medical need for many patients and their families. Approved treatments are restricted by poor survival and harsh side effects," stated Adam M. Brufsky, MD, PhD, FACP, Professor of Medicine at the University of Pittsburgh School of Medicine and Medical Director of the Magee-Women’s Cancer Program. "We are impressed with BriaCell’s promising randomized Phase 2 survival data indicating robust survival and a preferred tolerability profile for Bria-IMT and look forward to seeing the data being replicated in BriaCell’s pivotal Phase 3 study."

"A number of patients with metastatic breast cancer have disease progression on currently approved drugs, including CPIs and ADCs, with limited overall survival," remarked Dr. Aditya Bardia, Program Director of Breast Medical Oncology at UCLA, who was not involved with the BriaCell Phase 2 clinical trial. "BriaCell’s clinical data is interesting and highlights the role of the combination of Bria-IMT with CPIs in MBC."

"Significant numbers of patients with metastatic breast cancer do not respond to currently approved drugs, including CPIs and ADCs, and have a very limited lifespan of weeks to a few months," said Dr. William V. Williams, BriaCell’s President and CEO. "BriaCell’s clinical data supports our hypothesis that our regimen has prolonged survival in patients with metastatic breast cancer who otherwise have not responded to currently available treatments. We look forward to further confirming these impressive data in our ongoing pivotal Phase 3 study, with interim results expected in the second half of 2025. Overall survival is the primary endpoint in our pivotal Phase 3 study."

Table 1: Comparable Analysis of 1 year survival for the BriaCell Phase 2 study

Reference Breast Cancer Type Median prior lines of therapy Median OS (months) Percent Survival at 1 year
Bria-IMT plus CPI All types
61% HR+
33% TNBC
6% HER2+ 6 13.4*
15.6** 55%
Cortes et al.1 All types
57% HR+
18-19% TNBC
18-20% HER2+ 4 9.1-9.3 ~38-40%
Kazmi et al.2 All types
51-52% HR+
25-29% TNBC
9-24% HER2+ 2 7.2-9.8 30-38%
Bardia et al.
(TPC arm)3 TNBC 2-3 6.9 ~23%
Rugo et al
(TPC arm)4

HR+ HER2- 2 11.2 47%
* Patients treated with the Phase 3 formulation
** Patients treated with the Phase 3 formulation since 2022

Cortes J, et al. Annals of Oncology 2018
Kazmi S, et al. Breast Cancer Res Treat. 2020
Bardia A, et al. J Clin Oncol. 2024
Rugo HS, et al. The Lancet. 2023
Abbreviations:
HR+: hormone receptor-positive
TNBC: Triple-negative breast cancer (lacks or has low levels of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2))
HER2+: Human epidermal growth factor receptor 2 positive
HR+ HER2-: hormone receptor-positive and human epidermal growth factor receptor 2 negative
TPC: Treatment of Physicians Choice

The Phase 2 study enrolled 54 heavily pre-treated metastatic breast cancer patients (median number of prior treatments = 6) who received the Bria-IMT regimen plus checkpoint inhibitor. Of these 54 patients, 37 were treated with the formulation currently being used in BriaCell’s ongoing pivotal Phase 3 study in metastatic breast cancer (listed on ClinicalTrials.gov as NCT06072612). Final median overall survival calculation for the Phase 2 study is pending, as many patients remain alive. No Bria-IMT related discontinuations have been reported to date.