On April 4, 2023 Nerviano Medical Sciences Srl (Company), a member of NMS Group and a clinical stage company discovering and developing innovative therapies for the treatment of cancer, reported that data from the Phase I/II clinical study of NMS-03592088 in Acute Myeloid Leukemia will be reported in an oral presentation by Dr. Antonio Curti, MD, PhD, IRCCS Azienda Ospedaliero-Universitaria di Bologna, at the upcoming AACR (Free AACR Whitepaper) Annual Meeting which will be held April 14 – 19, Orange County Convention Center, Orlando, Florida (Press release, Nerviano Medical Sciences, APR 4, 2023, View Source [SID1234629806]).

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Details of the upcoming oral presentation are as follows:

Title: NMS-03592088, a novel, potent FLT3, KIT and CSF1R inhibitor with activity in FLT3 positive acute myeloid leukemia patients with prior FLT3 inhibitor experience
Presenter: Dr. Antonio Curti, Istituto di Ematologia Seràgnoli, IRCCS Azienda Ospedaliero-Universitaria di Bologna
Session: CTMS01 – Novel Clinical Trials for Hematological Malignancies- CT025
Session Date/Time: April 16, 2023, 4:05 PM – 4:15 PM
Location: Valencia A – Convention Center

The data are embargoed until the day of the presentation. A copy of the oral presentation will be available at www.nervianoms.com following presentation at the meeting.
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About NMS-03592088

Acute Myeloid Leukemia (AML) is a rapidly progressing hematologic malignancy that most frequently develops in older adults. FLT3 mutations occur in approximately 30% of AML patients and are associated with aggressive disease, higher relapse rates and worse survival. Despite the approval of FLT3 inhibitors midostaurin and gilteritinib that improve the treatment of FLT3 positive patients, the prognosis of patients with relapsed or refractory disease is poor.

NMS-03592088 is a novel, potent inhibitor of FLT3, KIT and CSF1R, all relevant targets in AML. NMS-03592088 showed superior preclinical activity compared with approved FLT3 inhibitors in different FLT3-driven models. In addition, NMS-03592088 is active on FLT3 gatekeeper mutation F691L causing resistance to first generation FLT3 inhibitors.

MKIA-088-001 is a Phase I/II study of NMS-03592088 administered as single agent in relapsed or refractory AML and CMML patients. The trial is currently open for enrollment.

On April 4, 2023 Mythic Therapeutics, a biotechnology company focused on the development of next-generation antibody-drug conjugate-based therapies for the treatment of a wide range of cancers, reported that the first subject has been dosed in the Phase 1 KisMET-01 clinical trial of MYTX-011 (Press release, Mythic Therapeutics, APR 4, 2023, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-announces-first-subject-dosed-in-phase-1-kismet-01-clinical-trial-of-cmet-targeting-antibody-drug-conjugate-adc-mytx-011-for-the-treatment-of-non-small-cell-lung-cancer-nsclc [SID1234629805]). MYTX-011 is a cMET-targeting ADC being investigated for the treatment of patients with locally advanced, recurrent or metastatic non-small cell lung cancer (NSCLC).

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"Today’s announcement of our first subject dosed represents a significant step towards increasing the number of lung cancer patients eligible for treatment using ADCs, including those whose cancers express moderate cMET levels," said Brian Fiske, PhD, Chief Scientific Officer and Co-Founder at Mythic Therapeutics. "At Mythic, we are focused on our vision of unlocking the full potential of MYTX-011 as well as our broader pipeline of ADCs incorporating FateControl technology, which represents a fundamentally new paradigm for ADC therapies."

The KisMET-01 Phase I clinical trial is an open-label, multi-center, dose escalation and dose expansion study that will evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of MYTX-011 in subjects with locally advanced, recurrent or metastatic NSCLC. The study will be conducted in two parts. Part 1 will assess the safety and tolerability of MYTX-011 and identify the dose(s) to be studied in Part 2. Part 2 will include subjects with NSCLC with cMET overexpression or MET amplification/exon 14 skipping mutations, which are currently populations with an unmet medical need.

MYTX-011, a cMET-targeting ADC, leverages Mythic’s innovative FateControl technology, which allows ADCs to actively navigate inside of cells to potentially increase delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles.

The first patient was dosed at Sarah Cannon Research Institute (SCRI) at Tennessee Oncology in Nashville, Tennessee, under the care of Melissa Johnson, MD, Director, Lung Cancer Research, SCRI. "Although ADCs have been around for decades, their clinical benefit has been limited to a subset of diseases and targets with specific characteristics, such as high levels of target expression," said Dr. Johnson. "With cMET overexpression occurring in up to 70% of NSCLC tumors,[1],[2] patients need better treatment options to address lower levels of cMET target expression. We look forward to evaluating the potential of MYTX-011 to expand the use and eligibility of ADCs for patients with NSCLC."

More information about the clinical trial is available at clinicaltrials.gov (identifier: NCT05652868).

On April 3, 2023 Biodexa Pharmaceuticals PLC (AIM: BDRX.L; Nasdaq: BDRX), a drug delivery technology company focused on improving the bio-delivery and bio-distribution of medicines, reported that, in accordance with the terms of previously issued Pre-Funded Warrants and the associated Price Adjustment Mechanism under the Private Placement, it has issued an additional 10,508,394 Pre-Funded Warrants, calculated by dividing the aggregate subscription amount by 90% of the average of the daily volume weighted average prices of the five trading days prior to the date of this announcement (Press release, Midatech Pharma, APR 4, 2023, View Source [SID1234629804]). The issue of such Pre-Funded Warrants results in the total number of Pre-Funded Warrants issued under the Private Placement being 12,444,558, accounting for the Company’s completed Consolidation and Ratio Change, as detailed in its circular dated 7 March 2023

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Each Pre-Funded Warrant is immediately exercisable into one new ADS (equivalent to five new Ordinary Shares) with an exercise price of US$0.0004.

On April 4, 2023 Absci Corporation (Nasdaq: ABSI), a generative AI drug creation company, and M2GEN, an oncology bioinformatics company with the most advanced lifetime-consented clinicogenomics data to accelerate discovery research, reported a partnership to create new cancer medicines and bring them to market at unprecedented speed (Press release, M2Gen, APR 4, 2023, View Source [SID1234629803]). Absci’s generative AI drug creation platform will tap into M2GEN’s clinical and molecular data set, ORIEN AVATAR (AVATAR), to accelerate the creation of therapeutics for a range of malignancies and patient profiles, bringing AI drug creation to the fight against cancer.

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A key challenge in creating effective cancer treatments is finding specific antigens that can be targeted by immunotherapies. M2GEN’s AVATAR database represents a valuable resource for discovering such antigens. Absci will use its reverse immunology technology to first search the database for antibodies from patients with exceptional immune responses, then computationally re-assemble antigen-antibody pairs as promising starting points for drug development.

This partnership brings together AI drug creation technology and oncology bioinformatics to potentially reduce the time and cost to create better cancer treatments. Absci’s Integrated Drug Creation platform unites generative AI and wet-lab capabilities to screen billions of cells per week, allowing it to go from AI-designed antibodies to lab-validated candidates in as little as six weeks. As the nexus between patients, researchers, and the pharmaceutical industry, M2GEN is uniquely positioned and equipped with the richest clinicogenomic data set, and a lifetime patient-consented Total Cancer Care (TCC) protocol, to accelerate drug discovery and development and transform how cancer is treated. M2GEN’s real-world data set comes from its Oncology Research Information Exchange Network (ORIEN) partners, an alliance of 18 cancer centers across more than a dozen U.S. states.

"M2GEN and its ORIEN partners are premier leaders in the field of oncology data research and bring a wealth of unique data sets to our generative AI platform that may enable us to ultimately shave years off the drug discovery process," said Sean McClain, CEO of Absci. "This is an important leap forward to better understand individualized protein-protein interactions on cancer cells, moving us toward delivering on the promise of personalized medicine."

The cornerstone of ORIEN is the lifetime-consented TCC protocol, one of the first longitudinal cancer patient databases of its kind, with over 360,000 patients enrolled nationwide. TCC enables patient monitoring throughout their treatment journey, with the goal to transform how cancer is treated. M2GEN and ORIEN research-facilitated projects are monitored by a multi-institution governing body, which includes scientists and research leaders from network members, to ensure adherence to privacy protocols and best practices.

"Absci’s recent breakthrough creating de novo antibodies changed the idea of what’s possible for drug discovery," said Jim Gabriele, CEO of M2GEN. "This was just one of the things that excited us about partnering together. Their AI-led approach to targeting biologics to make the drug discovery process more efficient and dramatically impact patients’ lives made them an ideal partner," said Gabriele. "Together, by utilizing our real-world data, we plan to advance personalized cancer treatments in pursuit of a cure."

This partnership maintains Absci’s momentum building one of the largest repositories of patient data in the industry to train its generative AI platform for protein drug creation. The company recently partnered with St. John’s Cancer Institute to train on their datasets to discover medicines faster.

On April 4, 2023 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported the presentation of new data for both of its pipeline molecules, paxalisib and EVT801, at the upcoming Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), held in Orlando, FL, from 14 – 19 April 2023 (Press release, Kazia Therapeutics, APR 4, 2023, View Source [SID1234629801]).

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In total, there will be five presentations at AACR (Free AACR Whitepaper), four of which build on previous positive data for paxalisib in melanoma and childhood brain cancer. The new data being presented provide significant support and direction for the future development of paxalisib in these expansion indications.

In addition, a presentation by scientists from Kazia’s partner, Evotec, will outline the novel biomarker strategy employed in the phase I study of EVT801, and anticipates the potential initial clinical data from EVT801 in CY2023.

Key Points

Research by Dr Gennie Parkman and colleagues, working in the laboratory of Professor Sheri Holmen at the Huntsman Cancer Institute at the University of Utah in Salt Lake City, shows paxalisib leading to ‘substantially increased overall survival’ in a mouse model of BRAF-driven melanoma.

Further data from Dr Tyler Findlay and Dr Kristen Malebranche in Professor Jeffery Rubens’ team at Johns Hopkins University Medical School has shown compelling evidence of synergy between paxalisib and both gemcitabine, a chemotherapy agent, and mirdametinib, a targeted therapy, in animal models of atypical teratoid / rhabdoid tumors (AT/RT), a childhood brain cancer. This data expands on positive data for paxalisib as monotherapy and in other combination regimens that was presented at AACR (Free AACR Whitepaper) in 2022. The results suggest potential therapeutic approaches for use in clinical trials.

An additional abstract by Dr Hyuk Jean Kwon and colleagues at Professor Rubens’ lab describes in vitro preclinical data for the combination of paxalisib with a dual inhibitor of ACVR1 and MEK in diffuse midline gliomas, a category of childhood brain cancers which includes DIPG. The data showed strong synergy between the two agents, and points to further research in this area.

A poster presentation by Dr Michael Paillaisse and colleagues at Evotec SE describes some of the novel biomarker selection strategies employed in the ongoing phase I study of EVT801 in advanced solid cancers (NCT05114668). The poster outlines the approaches taken by the Evotec team to identify VEGFR3 expression in a range of tissues, potentially allowing for the selection of clinical trial patients who are likely to be more responsive to EVT801.

"The broad range of abstracts presented at AACR (Free AACR Whitepaper) speak to the breadth of work that is ongoing across our pipeline," said Dr James Garner, Chief Executive Officer of Kazia. "The promising new data from Professors Holmen and Rubens, in melanoma and childhood brain cancer respectively, reinforces the significance of these new opportunities for paxalisib. Moreover, Kazia’s ongoing collaboration with Evotec remains extremely fruitful, with excellent work from the biomarker team opening the possibility of rational patient selection in clinical trials. Of note, biomarker strategy is an important area of focus for FDA, and drug candidates with biomarker selection are potentially more likely to achieve approval than those without."

Summary of Abstracts

SESSION PO.ET03.02 – Drug Resistance in Molecular Targeted Therapies 2

April 16, 2023 – 1:30pm-5:00pm

Abstract 427/22 – Newer generation mTOR inhibition represents effective therapeutic strategy for BRAF-mutant melanoma

Gennie L Parkman, Tursun Turapov, David Kircher, William Burnett, Christopher Stehn, Kayla O’Toole, Katie Culver, Ashley Chadwick, Riley Elmer, Ryan Flaherty, Mona Foth, Karly Stanley, Robert Andtbacka, David Lum, Robert Judson-Torres, Martin McMahon, Sheri Holmen

Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

University of Minnesota, Minneapolis, MN

SESSION PO.CL09.01 – Combination Therapies for Cancer

April 18, 2023 – 1:30pm-5:00pm

Abstract 5490/8 – Combination of the PI3k inhibitor paxalisib with the nucleoside analog Gemcitabine over-activates the integrated stress response and induces atypical teratoid / rhabdoid tumor cell death

Tyler Findlay, Kristen Malebranche, Anupa Geethadevi, Eric Raabe, Charles Eberhart, Jeffrey Rubens

Johns Hopkins University School of Medicine, Baltimore, MD

Abstract 5509/27 – The PI3K inhibitor paxalisib combines synergistically with the MEK inhibitor mirdametinib to target atypical teratoid / rhabdoid tumors

Kristen J. Malebranche, Tyler Findlay, Anupa Geethadevi, Charles Eberhart, Eric Raabe, Jeffrey Rubens

Johns Hopkins University School of Medicine, Baltimore, MD

SESSION PO.ET01.04 – Targeting Protein Kinases and Phosphatases for Therapy 1

April 18, 2023 – 1:30pm-5:00pm

Abstract 4990/3 – Dual inhibitor of ACVR1 and MEK 1/2 E6201 and PI3K/mTOR inhibitor paxalisib synergistically inhibit cell growth in DMG

Hyuk Jean Kwon, Abigail Tindall, Charles Eberhart, Jeffrey Rubens, Eric Raabe

Johns Hopkins University School of Medicine, Baltimore, MD

SESSION PO.CL01.06 – Diagnostic and Prognostic Biomarkers 1

April 16, 2023 – 1:30pm-5:00pm

Abstract 1015/25 – VEGFR-3 expression profiling by histology to classify patient population for the selective VEGFR-3 inhibitor EVT801

Michael Paillasse, Pierre-Benoit Ancey, Gaelle Badet, Anne Gomez-Brouchet, Janik Selves, Philippe Rochaix, Maxime Battistella, Celeste Lebbe, Philippe Cassier, Carlos Gomez-Roca, Jean-Pierre Delord, Mark Whittaker, Lise Davenne, John Friend, Michael Fitzgerald, James Garner, Pierre Fons

Evotec SE, Toulouse, France & Abingdon, UK

Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France,

Université de Paris Cité, AP-HP Hôpital Saint Louis, Paris, France,

Centre Léon Bérard, Lyon, France

Kazia Therapeutics Ltd, Sydney, Australia