On December 9, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with solid tumors or hematologic malignancies, reported initial positive clinical data from the multi-center Phase 1-2 study of IMPT-314 in patients with large B-cell lymphoma that is being presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Lyell Immunopharma, DEC 10, 2024, View Source [SID1234648922]). IMPT-314 is an autologous dual-targeting CD19/CD20 chimeric antigen receptor (CAR) T-cell product candidate being developed for patients with aggressive B-cell non-Hodgkin lymphoma.

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As of October 22, 2024 (the data cutoff for the presentation), 23 patients with relapsed or refractory (R/R), CAR T-naive large B-cell lymphoma received IMPT-314. The efficacy evaluable population consisted of 17 patients. The ORR was 94% (16/17 patients), with 71% (12/17 patients) achieving a CR by three months. The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients were in response at last follow-up). In the safety evaluable population of 23 patients, no Grade 3+ CRS was reported. Grade 3 ICANS was reported in 13% (3/23) of patients with a median time to complete ICANS resolution of 5 days, and rapid improvement to Grade 2 or lower with standard therapy. In the efficacy evaluable set, 16 patients were evaluable for pharmacokinetics. IMPT-314 demonstrated robust expansion and peak cell expansion occurred between Days 7 – 28 post IMPT-314 infusion (median Tmax = 10 days). Additionally, the final drug product contained the desired naïve and central memory cell phenotype (median, 91%; range, 82 – 99%) that has been associated with improved overall survival in other CAR T cell clinical studies.

The data are being presented today at the 2024 ASH (Free ASH Whitepaper) Annual Meeting by Sarah M. Larson, M.D., Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, and the poster is available in the Investors’ section of the Company’s website.

"The high rate of complete responses with a favorable safety profile support the strong potential of IMPT-314, Lyell’s next-generation dual-targeting CAR T-cell therapy enriched for naïve and central memory T cells. This product candidate was designed to maximize durable responses by overcoming heterogeneous CD19 antigen density and antigen escape, enhance CAR T cell persistence, and reduce exhaustion," said Lynn Seely, M.D., Lyell’s President and Chief Executive Officer. "Based on these strong data, we remain on track to initiate a pivotal trial in 2025 of IMPT-314 in CAR T-naive patients with large B-cell lymphoma in the 3rd-line+ setting and are continuing to evaluate IMPT-314 in the 2nd-line setting in the ongoing Phase 1-2 trial."

"The data presented today from IMPT-314 suggest the potent targeting of both CD19 and CD20 coupled with CD62L+ cell enrichment has the potential to provide differentiated benefit in objective and complete response rates over first-generation CD19 CAR therapies in patients with aggressive large B-cell lymphoma," stated Sarah M. Larson, M.D., Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA. "IMPT-314 incorporates the same CAR construct as CART19/20 which was evaluated in a Phase 1 trial at UCLA, and I am pleased that the IMPT-314 data are consistent with our experience at UCLA."

About IMPT-314

IMPT-314 is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the response as compared to the approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma.

IMPT-314 is designed with an ‘OR’ logic gate to target B cells that express either CD19, CD20 or both. IMPT-314 is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a proprietary process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity.

IMPT-314 has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of relapsed/refractory aggressive B-cell lymphoma.

On December 10, 2024 ALX Oncology Holdings Inc. ("ALX Oncology" or "the Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing therapies that boost the immune system to treat cancer and extend patients’ lives, reported results from a Phase 1b/2 clinical trial demonstrating the company’s investigational CD47-blocker evorpacept in combination with Jazz Pharmaceuticals’ zanidatamab generates promising anti-tumor activity in patients with both HER2-positive and HER2-low advanced breast cancer (Press release, ALX Oncology, DEC 10, 2024, View Source [SID1234648973]). The findings, which are the first from a clinical trial evaluating the safety and efficacy of evorpacept and zanidatamab in heavily pretreated patients with metastatic breast cancer (mBC), will be presented on Thursday, December 12 in a poster spotlight presentation (#PS8-09) at the 2024 San Antonio Breast Cancer Symposium (SABCS).

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"These data suggest that HER2-positive patients whose cancer has been heavily pretreated may benefit from CD47 inhibition via evorpacept’s unique mechanism when combined with a HER2-targeted agent," said Alberto J. Montero, M.D., MBA, Clinical Director, Breast Cancer Medical Oncology Program, Case Western Reserve University, and the study’s principal investigator. "New therapeutic options with better safety profiles are desperately needed for these patients, and this is particularly true once disease progresses following advanced, standard-of-care therapies such as ENHERTU."

The Phase 1b/2 open-label, multi-center clinical trial (NCT05027139) evaluated the potential of evorpacept, a highly differentiated, investigational CD47 blocker, in combination with zanidatamab, a dual HER2-targeted bispecific antibody, as a novel treatment for patients with previously treated inoperable, locally advanced, or metastatic HER2-expressing breast cancer and other cancers.

Part one of the trial evaluated the safety and recommended doses for the combination; part two assessed the anti-tumor activity of the resulting combination. The SABCS poster presentation will include efficacy findings from all three of the part-two trial cohorts: Cohort 1 (n=21) consisted of patients with HER2-positive breast cancer who had received a median of six prior systemic therapies in the metastatic setting. Notably, all patients in Cohort 1 had received prior fam-trastuzumab deruxtecan-nxki (ENHERTU). Patients were enrolled based on local assessment of tumor samples or central assessment. Of the 21 patients enrolled in Cohort 1, nine were found to be HER2-positive based on central assessment. Cohort 2 (n=15) consisted of patients with HER2-low breast cancer who had received a median of five prior systemic therapies. Cohort 3 (n=8) consisted of patients with other HER2-expressing cancers.

Key trial results to be shared at SABCS 2024 include:

HER2-positive by central assessment mBC: Patients in Cohort 1 who were HER2-positive by central assessment (n=9) showed the greatest anti-tumor activity with a confirmed objective response rate (cORR) of 55.6% and a median progression free survival (mPFS) of 7.4 months.
HER2-positive mBC: Overall, patients in Cohort 1 (n=21) had a confirmed cORR and mPFS of 33.3% and 3.6 months, respectively.
HER2-low mBC: Responses were also observed in Cohort 2 (cORR: 20.0%; mPFS: 1.9 months).
As of the August 2024 data cutoff, median follow-up was 9.6 months, with six patients still on treatment. The median duration of response was not reached for Cohort 1 patients (range: 3.6-25.9 months) and was 5.5 months for Cohort 2 patients (range: 3.6-11.0 months), with responses ongoing, including the longest observed response, in each cohort.
Most treatment-related adverse events were grade 1 or 2. The most frequent adverse events due to any cause were fatigue, nausea, diarrhea, and infusion-related reactions. There were no treatment-related deaths in the study and no non-infectious pulmonary toxicities. These safety findings are consistent with those observed in the >700 patients treated with evorpacept to date.

"This study adds to the growing body of evidence suggesting that evorpacept can treat HER2-positive cancers after patients progress on multiple conventional HER2-directed therapies, given that the encouraging response rate of 55 percent in this population would not be expected," said Jason Lettmann, Chief Executive Officer at ALX Oncology. "The data that will be presented this week also further validate our biomarker strategy, showing that confirmed HER2-expression drove the largest benefit for patients. Collectively, these findings provide us with the proof of concept necessary to accelerate our clinical plans to advance evorpacept in HER2-positive breast cancer."

A copy of the poster presentation will be available on the Publications section of ALX Oncology’s website at the start of the presentation at SABCS on December 12, 2024.

On December 10, 2024 Neogap Therapeutics AB, a Swedish clinical-stage biotechnology company, reported that the European Medicines Agency (EMA) has granted Advanced Therapy Medicinal Product (ATMP) classification to its cell therapy, pTTL (personalised Tumour Trained Lymphocytes) (Press release, Neogap Therapeutics, DEC 10, 2024, View Source,c4079677 [SID1234648989]). This classification confirms that pTTL meets the regulatory criteria for a somatic cell therapy product, providing a clear regulatory pathway for its further development.

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The ATMP classification is a key milestone for companies developing advanced therapies. It signifies that the EMA formally recognises the product as an advanced therapy under EU regulations. This designation offers access to the EMA’s tailored scientific advice, ensuring that the therapy’s safety, quality, and efficacy meet stringent regulatory standards. For Neogap, the classification sets a clear direction for preparing upcoming clinical trials and advancing towards future market authorisation.

Neogap’s personalised cell therapy is currently being evaluated in a Phase I/II clinical trial focused on assessing its safety and tolerability in patients with advanced colorectal cancer. This study is a critical step in Neogap’s mission to provide curative treatments for cancer patients with limited remaining treatment options.

"The ATMP classification is a strong validation of our innovative approach and pTTL’s potential as a breakthrough cancer therapy," says Samuel Svensson, CEO of Neogap Therapeutics. "It provides regulatory clarity and invaluable guidance from the EMA, enabling us to advance development efficiently and effectively. We are now well-positioned to continue our work towards delivering transformative treatments to cancer patients."

On December 10, 2024 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported that it has dosed the first patient in the IDEAYA-sponsored Phase 1 trial evaluating the combination of IDE161, the company’s investigational, potential first-in-class, small molecule poly (ADP-ribose) glycohydrolase, or PARG, inhibitor, in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in endometrial cancer patients with high microsatellite instability (MSI-high) and microsatellite stable(MSS) (Press release, Ideaya Biosciences, DEC 10, 2024, View Source [SID1234649005]).

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"We continue to progress our IDE161 program and are excited to have the first patient dosed evaluating IDE161 in combination with KEYTRUDA in MSI-high and MSS endometrial cancer patients. This trial is part of our overall IDE161 clinical combination strategy that is focused on high conviction rational combinations," commented Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

"We are continually looking for ways to improve outcomes for patients with MSI-high and MSS endometrial cancer, and PARG has shown promising potential as a precision oncology target in these settings. IDE161 has shown robust anti-tumor activity in preclinical models, and I look forward to evaluating IDE161’s impact on endometrial cancer patients in combination with KEYTRUDA," added Dr. Panos Konstantinopoulos, M.D., Ph.D., Director of Translational Research and attending oncologist in the Division of Gynecologic Oncology at Dana-Farber Cancer Institute, and an Associate Professor of Medicine at Harvard Medical School.

IDE161 is a potential first-in-class inhibitor of poly(ADP-ribose) glycohydrolase (PARG), a novel, mechanistically distinct target in the same clinically validated biological pathway as poly(ADP-ribose) polymerase (PARP). IDE161 has been granted two FDA Fast Track designations in platinum-resistant advanced or metastatic ovarian cancer patients having tumors with BRCA1/2 mutations, and in pretreated advanced or metastatic HR+, Her2-, BRACA1/2 mutant breast cancer.

Under the clinical trial collaboration and supply agreement, Merck will provide KEYTRUDA to IDEAYA, the sponsor of the Phase 1 clinical combination trial. IDEAYA and Merck each retain all commercial rights to their respective compounds, including as monotherapy or as combination therapies.

The safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE161 in combination with KEYTRUDA is being evaluated as an arm in IDE161-001 (NCT05787587), an IDEAYA-sponsored Phase 1 trial of IDE161 in solid tumors. The selection of an initial Phase 1/2 monotherapy expansion dose has been made in a priority tumor type based on adverse event (AE) profile and preliminary clinical efficacy observed.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On December 10, 2024 Tasca Therapeutics Corp. ("Tasca"), a biotechnology company leveraging a unique drug discovery platform that identifies and maps novel lipid-binding pockets on proteins to develop new medicines to treat human diseases, reported a $52 million Series A financing, co-led by Regeneron Ventures and Cure Ventures, with participation by Invus Group (Press release, Tasca Therapeutics, DEC 10, 2024, View Source [SID1234649022]). This funding will be used to advance Tasca’s novel drug discovery platform, progress its lead program, CP-383, into Phase 1/2 clinical proof-of-concept studies, and to expand its drug candidate pipeline.

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"We are excited to enter this next phase of company growth with financial support from such leading life science investors and the continued backing of our pioneering scientific co-founders – Xu Wu, Ph.D., David Fisher, M.D., Ph.D., and Duojia Pan, Ph.D.," said Milenko Cicmil, co-founder and chief executive officer of Tasca. "Our first development candidate, CP-383, is a unique first-in-class molecule demonstrating excellent efficacy across multiple cancer types and we are looking forward to progressing it into the clinic."

Named after the Italian word for "pocket," Tasca is harnessing the power of mass spectrometry-based proteomics, coupled with the use of proprietary reagents, to identify proteins that undergo a specific post-translational modification called auto-palmitoylation. The specific sites of auto-palmitoylation, once mapped and characterized, serve as unique binding sites for novel therapeutics that can be developed to modify the function of the target protein. The auto-palmitoylated proteins Tasca identified represent a rich source of druggable targets across a range of therapeutic indications.

Tasca’s most advanced drug candidate, CP-383, is a first-in-class molecule that has demonstrated robust anti-cancer activity in both in vitro and in vivo studies across a broad range of human cancers, and will initially be evaluated in small cell lung cancer, colorectal cancer, head and neck cancer, and brain cancer patients.

Expert Executive Leadership Team

Tasca’s executive leadership team brings decades of experience in drug discovery and development, as well as a successful history of launching and leading new biotechnology programs and start-ups. Tasca’s executives have held major roles at several big pharma companies, including Merck, AstraZeneca, Bristol Myers Squibb, and Novartis. Their deep understanding of oncology matched with drug development and business expertise will enable them to find creative solutions for challenges faced by early-stage biotechnology companies.

"I was immediately impressed by Tasca’s in vivo data, that combined with the amazing leadership that Milenko provides and backing of strong firms like Regeneron Ventures and Cure Ventures," said Praveen Tipirneni, M.D., and chairman of the board. "I look forward to bringing my Morphic Therapeutic experience to the Tasca team."

Added Dave Fallace, co-founder and managing partner at Cure Ventures: "We founded Cure Ventures to help develop curative technologies and Tasca is expanding the boundaries of science with the potential of their platform. The prospect of being able to drug previously undruggable targets in oncology and potentially other indications differentiates Tasca from the competition. We’re confident in their programs and look forward to supporting them as they advance their platform and pipeline."