On October 23, 2024 Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported the presentation of the first human imaging data validating the potential of MT1-MMP as a novel target in the treatment of cancer and demonstrating the positive properties of Bicycle Radionuclide Conjugates (BRC) for radiopharmaceutical use, as well as preclinical data demonstrating optimized BRC radioisotope delivery at the European Association of Nuclear Medicine (EANM) 2024 Congress in Hamburg, Germany (Press release, Bicycle Therapeutics, OCT 23, 2024, View Source [SID1234647331]).

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"Since our founding, our goal at Bicycle Therapeutics has been to leverage the power of our platform in areas where we can have the most impact for patients. Over the years, we have built a robust pipeline of oncology therapies that includes targeted drug conjugates, immuno-oncology agents and now, radiopharmaceuticals," said CEO Kevin Lee, Ph.D. "The exciting data presented at EANM underscore the potential of our Bicycle Radionuclide Conjugates to deliver a range of isotopes to novel cancer targets. Through our strategy of pursuing novel targets with first-in-class potential and selecting the isotope that best aligns with the target biology and indication, we have an opportunity to potentially broaden the use of radiopharmaceuticals to diagnose and treat cancer."

In line with Bicycle Therapeutics’ radiopharmaceuticals strategy, the company selected tumor antigen EphA2 as its second BRC target and signed a letter of intent with leading isotope technology company Eckert & Ziegler to put in place an agreement to supply a range of radioisotopes and develop and manufacture BRC molecules. Bicycle Therapeutics, through its internal pipeline of wholly owned molecules and strategic collaborations with industry and academic leaders in the field, aims to be at the forefront of the development of next-generation radiopharmaceutical therapies. Bicycle molecules have ideal properties for radioisotope delivery due to their low molecular weight, high selectivity and affinity for their intended target and rapid systemic clearance.

"The data presented at EANM demonstrate how our Bicycle platform is a powerful tool for de novo identification of high-quality binders to important cancer targets. We believe the ability to optimize the biodistribution properties of our molecules, significantly reducing kidney retention while retaining rapid, selective uptake in tumors, position Bicycle Radionuclide Conjugates as a potentially best-in-class approach for targeted radionuclide therapy," said Michael Skynner, Ph.D., chief technology officer of Bicycle Therapeutics. "MT1-MMP is the first target for radiopharmaceutical development that we are pursuing given its expression in many solid tumors such as non-small cell lung cancer, esophageal and triple negative breast cancer."

EANM 2024 Congress Data Highlights

During an oral presentation, the German Cancer Consortium (DKTK) presented first human imaging data for a BRC targeting MT1-MMP. They focused on a case study in a 65-year-old male diagnosed with advanced pulmonary adenocarcinoma, the most common type of non-small cell lung cancer, in the lung and lymph nodes confirmed by endobronchial ultrasound (EBUS) biopsy. The patient received fluorine-18-labelled FDG-PET/CT imaging, and two weeks later received MT1-MMP PET/CT imaging up to one hour post injection of the gallium-68-labelled BRC tracer.

Both scans revealed multiple lymph node metastases and bone metastases in the sternum. MT1-MMP imaging demonstrated tracer uptake in the primary tumor in the lung and lymph node and bone metastases, consistent with FDG imaging. Additionally, the MT1-MMP BRC tracer showed renal excretion, with all other organs showing only negligible tracer uptake. Clear imaging contrast was also observed at early time points.

In an e-poster, Bicycle Therapeutics presented preclinical data demonstrating the suitability of Bicycle molecules to deliver indium to tumors in vivo due to their favorable properties, including specific tumor uptake, rapid tumor penetration and rapid renal elimination. Additionally, imaging showed how the biodistribution profile of BRCs can be optimized to maintain high tumor uptake and retention while significantly reducing kidney uptake and retention. These data build on the body of preclinical data the company has published in this area demonstrating the use of Bicycle molecules to effectively deliver various radioisotopes, such as lutetium and lead, to tumors.

Altogether, the data presented at EANM validate the potential of MT1-MMP as a novel target in the treatment of cancer, demonstrate the translatability of BRC preclinical data and highlight the potential of Bicycle molecules for targeted radionuclide therapy.

The e-poster, "Bicycle Radionuclide Conjugates for radioisotope delivery to solid tumors," is available in the Publications section of the Bicycle Therapeutics website.

Conference Call Details

Bicycle Therapeutics will host a conference call and webcast today, Oct. 23, at 8 a.m. ET to review the first human imaging data and outline the company’s radiopharmaceuticals strategy. To access the call, please dial 833-816-1408 (U.S.) or +1-412-317-0501 (international) and ask to join the Bicycle Therapeutics call. A live webcast and replay of the conference call will be accessible in the Investor section of the Company’s website at www.bicycletherapeutics.com.

On October 23, 2024 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of potentially best-in-class IL-2 therapeutics, reported data and analyses used to determine dose selection for Phase 2 expansion cohorts in a Phase 1/2 clinical trial of its lead candidate, AU-007 (Press release, Aulos Bioscience, OCT 23, 2024, View Source [SID1234647330]). The data and evaluations of pharmacodynamics, pharmacokinetics, safety and clinical efficacy were presented as a poster at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain.

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The results continue to affirm AU-007’s unique profile among interleukin-2 (IL-2) therapeutics, showing regulatory T cell (Treg) reduction, and demonstrating that deeper drops in peripheral Treg counts were associated with longer progression-free survival (PFS) outcomes in patients from the Phase 1 and Phase 2 portions of the AU-007 trial, across a range of dose levels, tumor types and lines of therapy. Additionally, increases in interferon-gamma and effector T cells (Teffs) were observed with escalating subcutaneously administered aldesleukin (recombinant human IL-2) dose levels.

"These data point to a correlation between deeper reductions in Tregs and better clinical outcomes, which differentiates AU-007 from all other IL-2 therapeutics in development," said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer. "We’re also excited about AU-007’s ability to increase Teffs and natural killer cells. These findings, combined with a mild and tolerable safety profile, further validate our belief in AU-007’s potential as a best-in-class IL-2 therapeutic for solid tumor cancers. We look forward to presenting new Phase 2 clinical efficacy and safety data, particularly in melanoma and renal cell carcinoma, later this year."

Created by Biolojic Design, AU-007 is the first human IgG1 monoclonal antibody designed by leveraging artificial intelligence to enter a human clinical trial. The antibody’s novel mechanism of action is to bind precisely to IL-2 instead of IL-2 receptors. By binding only to the portion of IL-2 that binds to CD25, AU-007 prevents IL-2 from binding to high-affinity IL-2 receptors on Tregs, vasculature and eosinophils, and redirects IL-2 to medium-affinity receptors on Teffs and natural killer (NK) cells. This allows Teffs and NK cells to expand and kill tumor cells.

Safety data presented at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium demonstrate manageable toxicity for AU-007 and low-dose, subcutaneous aldesleukin, with no vascular leak syndrome or pulmonary edema at all dose levels evaluated. Additionally, the AU-007 pharmacokinetic data show characteristics typical of an IgG1-LALA monoclonal antibody, with no evidence of neutralizing anti-drug antibody (ADA) activity and an approximate half-life of more than 15 days. No clear trends were observed in safety or efficacy data to determine if a single loading dose or multiple loading doses of aldesleukin would lead to better outcomes, and clinical investigation is ongoing in the Phase 2 dose expansion cohorts to determine the optimal dosing schedule.

Based on these results, researchers will evaluate dosing regimens of 9 mg/kg for AU-007 every two weeks (Q2W) and 135K IU/kg subcutaneous aldesleukin administered either on a single loading dose schedule or a Q2W multiple dose schedule in the Phase 2 expansion cohorts. The Phase 2 expansion portion of the trial is currently ongoing in renal cell carcinoma (RCC), melanoma and non-small cell lung cancer (NSCLC) evaluating these two dosing regimens.

The poster, "PB452: Determination of the phase 2 dose of AU-007, an AI-designed human monoclonal antibody that redirects IL-2 to T effector cells," (Abstract 464) is available to meeting registrants as an electronic poster on the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium’s online platform. It will be presented live in the poster session "New therapies in immuno oncology" on Friday, October 25, 2024, 9:00 a.m.-3:00 p.m. CEST in the Exhibition Hall.

The poster presentation is also available on the Aulos Bioscience website in the Abstracts and Publications section.

To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com.

About AU-007
AU-007 is a human IgG1 monoclonal antibody designed by leveraging artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 redirects IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

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.