On December 12, 2022 Step Pharma, the world leader in CTPS1 inhibition for the targeted treatment of cancer, reported that encouraging pre-clinical data on its first-in-class, highly selective, orally bioavailable CTPS1 inhibitor, STP938, were presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting held from the 10-13 December, 2022 in New Orleans, Louisiana and virtually (Press release, Step Pharma, DEC 12, 2022, View Source [SID1234625146]).
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The data presented by Step Pharma collaborators demonstrates the potential of STP938, a highly selective CTPS1 inhibitor, as a therapeutic for the treatment of mantle cell lymphoma and multiple myeloma both as a single agent and in combination with other targeted inhibitors.
In pre-clinical models of mantle cell lymphoma, STP938 showed strong anti-tumour effects, which were further enhanced by combined administration with venetoclax, a selective BCL-2 inhibitor currently in clinical development for treatment of this lymphoma type.
Single agent STP938 also showed activity in preclinical models of multiple myeloma and demonstrated strong synergy when combined with an inhibitor of the DNA damage response pathway (ATR, CHEK1 or WEE1).
"We are encouraged by the promising pre-clinical data produced by our collaborators showing the anti-tumour effects of STP938 in mantle cell lymphoma and multiple myeloma models",
said Andrew Parker, Chief Executive Officer of Step Pharma.
"These data reinforce our conviction that by inhibiting CTPS1, a key component of the pyrimidine synthesis pathway to which all cancers are addicted, STP938 has broad therapeutic potential. We have commenced clinical trials to test the safety and efficacy of STP938 in T cell and B cell lymphomas to bring this potentially lifesaving therapy to patients in our efforts to drive a step change in the way we treat cancer."
Full details of the poster presentations, which were both presented on Sunday, December 11, 2022 at 6:00 PM-8:00 PM EST in Hall D (Ernest N. Morial Convention Center), are:
Title: STP938, a Selective CTPS1 Inhibitor, Shows Single Agent Activity and Synergy with BCL2 Inhibition in Preclinical Models of Mantle Cell Lymphoma
Authors: David Chiron, PhD, Emmanuelle Menoret, PhD, Charlotte Kervoelen, PhD, Sophie Maïga, Celine Bellanger, Benoit Tessoulin, MD, Cyrille Touzeau, Hélène Asnagli, PhD, Andy Parker, PhD, Philip Beer, MD, PhD and Catherine Pellat-Deceunynck, PhD
Title: CTPS1 is a Novel Therapeutic Target in Multiple Myeloma that Synergizes with Inhibition of ATR, CHEK1 or WEE1
Authors: Christina Pfeiffer, MSc, Alexander Michael Grandits, PhD, Hélène Asnagli, PhD, Anja Schneller, MSc, Julia Huber, MSc, Niklas Zojer, MD, Martin Schreder, MD, Andrew Parker, PhD, Arnold Bolomsky, PhD, Philip Beer, MD, PhD, Heinz Ludwig, MD
Step Pharma also recently entered clinical development with STP938 in a Phase I/II trial for T cell and B cell lymphomas. An abstract outlining the study design was published by ASH (Free ASH Whitepaper) in the journal Blood. Full details are:
Title: A Phase 1/2 Study of STP938, a First in Class Inhibitor of CTP Synthase 1, in Patients with Relapsed/Refractory B or T Cell Lymphoma
Authors: Philip Beer, Maureen Higgins, Hélène Asnagli, Eef Hoeben, Michael Hubank, Andrew Parker, Brian Schwartz