On December 16, 2021 Forma Therapeutics Holdings, Inc. (Nasdaq: FMTX), a clinical-stage biopharmaceutical company focused on sickle cell disease, prostate cancer and other rare hematologic diseases and cancers, reported the company’s investigational oral, selective mIDH1 inhibitor combined with azacitidine yielded durable complete remission (CR) or CR with partial hematologic recovery (CRh) responses with favorable tolerability in patients with the mIDH1 form of acute myeloid leukemia (AML) (Press release, Forma Therapeutics, DEC 16, 2021, View Source [SID1234597301]).

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These positive findings, the first Phase 2 results of olutasidenib used in combination with a chemotherapy, were presented in an oral session on Dec. 13, 2021, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The findings support the potential of olutasidenib as the basis of combination therapy in patients with AML who have not achieved a durable response from prior therapy. In addition, a poster, presented on Dec. 12 at ASH (Free ASH Whitepaper), reported on the molecular characteristics of the mIDH1 of patients in the trial who responded to olutasidenib when administered as monotherapy.

"AML is a cancer that returns in about half of patients following initial treatment. Patients who are not achieving remission or suffer from an AML relapse are in need of new therapies with more durable outcomes. The data presented today at ASH (Free ASH Whitepaper) increase our understanding of olutasidenib’s potential to achieve durable complete responses when used as either first-line or second-line therapy along with a standard therapy for patients with mIDH1 AML," said Patrick Kelly, M.D., chief medical officer of Forma Therapeutics.

The oral presentation reports an analysis of four patient cohorts from the pivotal open-label Phase 2 arm of an ongoing Phase 1/2 study, (2102-HEM-101, NCT02719574), who received olutasidenib dosed 150 milligrams (mg) twice daily continuously during 28-day cycles plus azacitidine, as of June 16, 2021. Azacitidine, a hypomethylating agent (HMA), was administered daily as an intravenous or subcutaneous injection therapy for days one to seven of each cycle.

Investigators enrolled patients into one of the four groups based on their disease status and prior therapy and recorded the best overall response for the primary endpoint of a composite complete remission (CR) plus CR with partial hematologic recovery (CRh) rate (CR/CRh). The group of patients who had not yet received therapy for their AML and were candidates for azacitidine as a first-line treatment had CR/CRh rate of 45% (5 out of 11). The other three groups enrolled patients who had relapsed/refractory AML (R/R AML) that, respectively, had prior HMA therapy; had prior therapy with an IDH1 inhibitor, including olutasidenib monotherapy; and were candidates for azacitidine as a first-line treatment. The CR/CRh rates for these groups were 38% (5 of 13), 30% (6 of 20), and 47% (9 of 19), respectively.

Olutasidenib with Azacitidine Well Tolerated

Olutasidenib was well tolerated in the trial in combination with azacitidine and the combination had a safety profile largely consistent with that of olutasidenib alone. Treatment-emergent adverse events (TEAEs) occurring in 25 percent or more of the participants included nausea (49 percent), constipation (40 percent), vomiting (35 percent), thrombocytopenia (32 percent), diarrhea (28 percent), and neutropenia (26 percent). TEAEs of grade 3 or 4 in more than 10 percent of participants included neutropenia (26 percent), thrombocytopenia (25 percent), anemia (19 percent), and febrile neutropenia (14 percent). TEAEs of QTc prolongation occurred in five participants (7 percent), of whom two experienced grade 3 QTc prolongation, and none discontinued olutasidenib.

TEAEs associated with liver enzyme abnormalities occurred in 15 participants (21 percent), with grade 3/4 in six (8 percent). Investigator-assessed IDH1 differentiation syndrome in six (8 percent) patients, of whom most resolved with treatment interruption, dexamethasone, and/or supportive treatment, while two patients had concomitant leukocytosis.

Molecular Characteristics of Response to Olutasidenib in Patients with R/R AML

A poster presentation reported findings from a planned interim analysis of the trial’s cohort of patients with R/R AML receiving olutasidenib alone, dosed 150 mg twice daily. The analysis examined expression of IDH1m variant allele frequency, prevalence of other genetic co-mutations in the trial’s pivotal cohort, and associations between mutations and response. Responses were observed across all IDH1 mutation subtypes and response rates were lower amongst patients with concurrent FLT3 co-mutations. Patients with higher co-mutations at baseline had lower rates of response than those with low mutational burden. Similarly, patients with lower baseline IDH1 expression were more likely to respond than those with high expression.

Olutasidenib Presentations Details

Abstract 698: Olutasidenib (FT-2102) in Combination with Azacitidine Induces Durable Complete Remissions in Patients with mIDH1 Acute Myeloid Leukemia.

Session 616 on Monday, Dec. 13, at 3:00 PM ET

Presenter: Jorge E. Cortes, M.D.

Abstract 2351: Molecular Characteristics of Response to Olutasidenib (FT-2102) in Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia

Session: 616 on Sunday, Dec. 12, at 6:00 PM ET

Presenter: Stéphane de Botton, M.D., Ph.D.

For more information, please visit View Source or View Source

About AML

Acute myeloid leukemia (AML) is a cancer that starts in a person’s bone marrow but often quickly moves into the blood. AML develops from immature blood cells, known as myeloid cells, that are supposed to mature into white blood cells. However, the diseased myeloid cells do not function properly. They instead multiply rapidly, which causes normal blood cell production to fail. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that about 20,940 new cases, most in adults, arose in 2021 in the United States alone.1

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.2 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.3

About Olutasidenib

Olutasidenib is an oral, potent and small molecule investigational agent designed to selectively bind to and inhibit mutated IDH1 enzymes. This targeted treatment has the potential to provide therapeutic benefit by reducing 2-HG levels and restoring normal cellular differentiation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. When mutated, IDH1 activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 6 to 8 percent of patients with AML.

On December 16, 2021 Cullinan Oncology, Inc. (Nasdaq: CGEM) ("Cullinan"), a biopharmaceutical company focused on developing a diversified pipeline of targeted therapies for cancer patients, reported updated data from the Company’s ongoing Phase 1/2a trial of CLN-081 in non-small cell lung cancer (NSCLC) patients whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations that have progressed on or after prior therapy (Press release, Cullinan Oncology, DEC 16, 2021, View Source [SID1234597297]).

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"The updated data from our ongoing Phase 1/2a study in a larger number of patients further reinforce CLN-081’s differentiated clinical profile. CLN-081 has demonstrated both a high response rate and durable responses in heavily pre-treated patients," said Nadim Ahmed, Chief Executive Officer of Cullinan Oncology. "For many lung cancer patients currently receiving EGFR inhibitors, treatment related side effects can significantly impact their daily lives. In this regard, we are encouraged by CLN-081’s favorable safety profile at the 100mg BID dose."

The current analysis of the ongoing trial included a total of 73 NSCLC patients with EGFR exon 20 insertion mutations who received at least one dose of CLN-081 and were evaluable for safety as of the data cutoff. CLN-081 was administered orally, at dose levels including 30, 45, 65, 100 and 150 mg twice daily (BID). Based on prespecified safety and efficacy criteria, enrollment at the Phase 2a cohort for 100mg BID was expanded up to the planned maximum of 36 patients. Additional patients were also enrolled at the 150mg BID dose level, although enrollment was subsequently discontinued after a total of 11 patients based on overall assessment of the clinical profile at this dose level. Guided by these data,100mg BID was nominated as the Recommended Phase 2 Dose (RP2D) for CLN-081.

Efficacy Highlights:

Efficacy data from patients enrolled in the 100mg BID cohort:

Of 36 response evaluable patients, 14 achieved a confirmed PR for a 39% confirmed response rate and one additional patient had a PR that was pending confirmation at the time of the data cut-off.
The median duration of response was >15 months and the median progression free survival was 12 months in the initial cohort of phase 1 patients (N=13).
Safety and Tolerability Highlights:

Treatment related EGFR associated adverse event (AE) data for patients enrolled in the 100mg BID cohort:

Rash has been limited to Grade 1 and 2 events (54% and 18% of patients, respectively). Events were manageable with conventional supportive care and no patients have experienced Grade 3 or greater treatment-related rash.
Diarrhea has been limited to Grade 1 and 2 events (26% and 8% of patients, respectively). No prophylactic regimen has been required to ameliorate the incidence or severity of diarrhea to date, and no patients have experienced Grade 3 or greater treatment-related diarrhea.
"We are pleased with CLN-081’s safety and efficacy to date. CLN-081 has demonstrated antitumor activity among heavily pre-treated patients, including patients treated previously with other EGFR inhibitors or immunotherapy, and across a spectrum of exon 20 mutational sub-types," said Jon Wigginton, M.D., Chairman of the Cullinan Oncology Scientific Advisory Board and Senior Advisor. "We are similarly encouraged by the emerging durability data shown in this update, which we believe could also reflect the benefit of the drug’s favorable safety and tolerability profile. Our goal now is to review these results and potential future clinical development with the FDA and to move CLN-081 as expeditiously as possible into late-stage development."

Additional data are available in a presentation accompanying this press release on the Events section of our website.

About CLN-081

CLN-081 is an orally available, irreversible EGFR inhibitor that selectively targets cells expressing EGFR exon 20 insertion mutations while sparing cells expressing wild type EGFR. Cullinan is evaluating various doses of CLN-081 in a Phase 1/2a trial in patients with NSCLC harboring exon 20 mutations whose disease has progressed on or after prior therapy.

On December 16, 2021 Cellestia Biotech AG reported that the European Commission (EC) has granted CB-103 an orphan designation for the treatment of Acute Lymphoblastic Leukaemia (ALL) (Press release, Cellestia Biotech, DEC 16, 2021, View Source [SID1234597294]).

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This is the first Orphan Designation granted to CB-103. It is an important milestone in the development of CB-103, as it represents an official recognition from EMA that CB-103 looks promising in bringing significant benefit to those affected by ALL.

On December 16, 2021 BioCanRx’s network community, stakeholders and sponsors met virtually for the fifth Summit for Cancer Immunotherapy (Summit4CI) – BioCanRx’s annual scientific conference. Summit4CI brought together close to 400 attendees including leading scientists, clinicians, trainees, economists and representatives from industry, patient groups, charities and government (Press release, BioCanRx, DEC 16, 2021, View Source;utm_medium=rss&utm_campaign=successful-virtual-summit-cancer-immunotherapy [SID1234597291]).

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The Scientific Programming Committee organized a great agenda including plenaries on Advances in Cellular Immunotherapy, Approaches to Making Cold Tumors Hot and Advances in Pediatric Immunotherapy. The Oxford-style Debate focused on "Who is driving the CAR: NK cells vs T Cells." It was Dr. Jean-Sébastien "T cells rule" Delisle VS Dr. Michele "NK cells rock" Ardolino. After a lively debate, with strong arguments presented on both sides, the audience voted and declared Dr. Ardolino the winner.

Our network trainees took part in an HQP Development Day including a Meet the Experts lunch and more. Again this year, the scientific posters by our trainees were of a high calibre. Learn more about the HQP activities at the 2021 Summit4CI.

The BioCanRx-Cancer Stakeholder Alliance Learning Institute was back for its fourth edition at Summit4CI. It brought together four patient/caregiver leaders (Patient Scholars) and four Highly Qualified Personnel (Academic Scholars) in a series of virtual interactive Knowledge Exchange Sessions with the purpose of teaching patients/caregivers about the emerging and innovative concepts in immune-oncology and providing HQP an opportunity to learn from patients and get feedback about their research. Each Patient Scholar was paired with an Academic Scholar and the pairs presented key takeaways in plain language of the scientific Summit talks during the Knowledge Exchange Sessions.

The Learning Institute participants also took part in the Patient-Researcher Roundtable – a workshop-style event where Patient Scholars and funded BioCanRx Investigators discussed actionable ways to involve patient partners in their research programs. The event was facilitated by Drs. Manoj Lalu and Justin Presseau, of the Ottawa Hospital Research Institute, and included engagement by BioCanRx’s Cancer Stakeholder Alliance working group members. "With great discussions and conversation, the Learning Institute brings to light the importance of patient collaboration in research, as well as the translation of scientific information into plain language that is easily understood by all," said Dr. Stéphanie Michaud, President and CEO of BioCanRx.

BioCanRx also held a Public Forum titled ‘Understanding Cancer Immunotherapy Clinical Trials in Canada: Are they Needed Now More than Ever?’ Speakers included a clinical trial doctor, a patient partner who has participated in a clinical trial and a scientist who spoke about the latest developments in immunotherapy cancer research and treatments. You can watch the forum here.

Many thanks to our Scientific Programming Committee and all our Summit4CI speakers, the HQP Working Group and our Learning Institute organizers. A big thank you to our 2021 sponsors and exhibitors – we could not hold the Summit without your strong support!

BioCanRx’s Summit4CI Speaker Series will be resuming in the new year! Stay tuned to the Summit4CI website cancersummit.ca or biocanrx.com for announcements.

We hope you’ll save the date for next year’s Summit4CI! We’ll be meeting ‘in-person’ in Montreal at the Fairmont The Queen Elizabeth Hotel – November 19 – 21, 2022!

On December 16, 2021 invIOs (innovative Immuno-Oncology) GmbH, a privately held biotechnology company developing novel therapies for cancer, reported it will commence operations on 1 January 2022 (Press release, Apeiron Biologics, DEC 16, 2021, View Source [SID1234597288]).

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invIOs, a fully owned subsidiary of APEIRON Biologics AG has been assigned APEIRON’s innovative cancer immunotherapy activities and all related clinical and preclinical R&D projects.

invIOs’ CEO Peter Llewellyn-Davies and his management team have taken this step to realize the full potential of its cutting-edge development projects and to create an early clinical-stage focused entity to allow investors to benefit from significant upside potential, especially specialized international biotech investors.

The proprietary cell therapy technology platform for the modulation of intracellular Immuno-Oncology targets enables rapid treatment of patients using their own cells with short out-of-body time in an out-patient setting. The groundbreaking concept allows access to indications that have previously not been addressable by earlier cell therapy approaches.

The first clinically validated target is the immune master-checkpoint Cbl-b; the clinicalstage lead candidate APN401 will show results in the near term on safety with data from an ongoing Phase 1b trial to be finalized in Q2 2022. A discovery pipeline with two additional promising candidates could give rise to new effective therapies for cancer patients, namely INV441 aiming to activate TILs (tumor-infiltrating lymphocytes) in solid tumors and INV501, an oral small molecule for tumor specific immune activation.

Peter Llewellyn-Davies, CEO of invIOs, comments: "Our passion is to develop life-saving therapies for patients suffering from cancer where there currently exist only limited treatment options. invIOs’ highly experienced team has a proven track-record of taking drugs to market with a core competency in immuno-oncology. The new company is geared towards enabling innovation and growth and will facilitate access to funding from specialized investors and partners. invIOs’ novel approach represents an investment opportunity with significant upside potential and important benefits for healthcare professionals and patients."

invIOs is headquartered in Vienna, Austria and will streamline the development of novel therapies in immuno-oncology backed by the acumen of the existing team. Accordingly, all current APEIRON employees are assigned to invIOs.