On December 13, 2022 Tactical Therapeutics, Inc. (TTI), a clinical stage biopharma, reported that it has been selected to present at the MedInvest Oncology Investor Conference taking place December 14-15, 2022, in New York, NY (Press release, Tactical Therapeutics, DEC 13, 2022, View Source [SID1234625226]).

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"We are honored to be selected to present at this unique event," said Rashida Karmali, Ph.D., CEO of Tactical Therapeutics. "We welcome the chance to interact with many of the world’s most accomplished leaders and investors who are all dedicated to improving the health and lives of patients with glioblastoma (GBM) and difficult to treat solid cancers."

About Glioblastoma, recurrent (rGBM) and newly diagnosed (nGBM)
Glioblastoma, the brain tumor that killed Senator Ted Kennedy, Beau Biden and Senator John McCain, is still mostly untreatable. Recent reports suggest veterans of Vietnam, Iraq and Afghanistan wars who were exposed to burn pits later developed GBM. GBM exhibits debilitating neurological symptoms and suicide rates for GBM patients are higher compared to those with other cancers.

Since 2005, GBM, an orphan disease (approximately 18,000/yr), has a median overall survival (OS) of between 12 to 20 months in newly diagnosed GBM with surgery, radiotherapy (with temozolomide) and adjuvant temozolomide, plus tumor treating fields. rGBM recurs frequently within a year with a median OS of 10 months.

TTI’s oral, safe and brain-penetrating drug, Carboxyamidotriazole Orotate (CTO), showed efficacy with significantly improved OS from 10 months to 28 months+ in nGBM in Phase IB trial, with published results (J. Clin Oncology, (2018)36:1702-1709).

Dr. Antonio Omuro, who oversaw the CTO Phase I clinical trial, had this to say about the promising treatment:

"In 27 Recurrent GBM patients, 1 complete and 6 partial responses were observed in patients who had been in several previous trials, including patients previously exposed to bevacizumab, who are the most challenging patients to treat. Radiographic responses are rarely seen in glioblastoma trials, therefore these are really promising results. Excellent survival was observed in 15 newly diagnosed GBM (13/15), with median overall survival not reached after 28 months; 2-year survival 62%; 1-year survival 93%. Two patients remain recurrence free at 5 years.

"The safety profile was excellent, and we were also able to demonstrate that CTO crosses the blood brain barrier and can achieve high concentrations in brain tumors. Overall, the Phase IB trials of CTO in GBM patients showed highly promising efficacy and safety in patients with very advanced disease."

About Carboxyamidotriazole Orotate (CTO) & Intellectual Property (IP)
CTO is a patented first-in-class inhibitor of genes of non-voltage dependent calcium signaling associated with multiple oncolytic pathways and calcium channels. At clinically relevant CTO levels, differential expression of some mRNA showed inhibition of transcriptional signatures of several oncogenes, and in contrast activation of tumor suppressors.

The IP portfolio includes 8 U.S. and 75 International patents lasting to 2033.

On December 13, 2022 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported that the U.S. Food and Drug Administration (FDA) has provided a safe to proceed letter and cleared the IND application for VIP236, the Company’s front-runner SMDC for the treatment of advanced solid tumors (Press release, Vincerx Pharma, DEC 13, 2022, View Source [SID1234625225]).

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VIP236 is a first-in-class SMDC with a tailored design to efficiently treat patients with cancer with aggressive and metastatic disease. VIP236 binds to activated αVβ3 integrin allowing specific homing to the tumor and is efficiently cleaved by neutrophil elastase (NE). Both proteins are present in the tumor microenvironment (TME), are highly expressed in advanced metastatic tumors, and are associated with poor prognosis in patients with cancer. Anticancer activity occurs after a specific and targeted release of an optimized camptothecin (CPT) payload by NE in the TME. The CPT payload of VIP236 is optimized for high permeability with low active efflux potential to overcome transporter-mediated resistance observed with SN38, the active metabolite of irinotecan.

"We are excited to advance our lead SMDC, VIP236, to the clinic," said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx. "Preclinical results provide validation of our targeting mechanism and demonstrate how VIP236 can deliver up to 40 times more drug to the cancer than the surrounding tissues or normal organs. This is evident in the durable tumor regressions and significant reduction of metastases in patient-derived xenograft (PDX) cancer models, including PDX models of triple negative breast cancer, renal cell carcinoma and colorectal cancer."

Dr. Hamdy continued, "We look forward to starting our first-in-human dose- escalation study early next year to evaluate the maximum tolerated dose, safety and tolerability in patients with advanced or metastatic solid tumors. Bringing VIP236 to the clinic while continuing to be strategic about our resources remains one of our top priorities. We will be pushing the VIP236 program forward into Phase 1 with our existing capital and continue to expect our cash runway to lead us into late 2024."

On December 13, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), reported positive results from its ongoing dose escalating Phase 1 first-in-human study of its highly selective CDK9 inhibitor, GFH009, in patients with relapsed and/or refractory (r/r) hematologic malignancies (Press release, Sellas Life Sciences, DEC 13, 2022, View Source [SID1234625224]). Results include preliminary safety and efficacy data presented this week at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, along with updated data since the ASH (Free ASH Whitepaper) abstract cutoff date of August 2, 2022.

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One patient treated with GFH009, in the 30 mg once per week cohort, achieved a confirmed complete response (CR), which is the first CR reported in acute myeloid leukemia (AML) with any CDK9 inhibitor monotherapy. No minimal residual disease (MRD) was detected in this CR patient and full neutrophil, platelet and red blood cell recovery was reported. Anti-cancer effects were also observed at multiple dose levels in both the r/r AML and r/r lymphoma treatment groups. Neutrophil counts improved in most patients from both groups while on treatment, and drug-related severe neutropenias were observed in less than 10% of enrolled patients. Dose limiting toxicities have not been identified at any of the levels studied to date and the maximum tolerated dose has not yet been reached.

"We are excited to see a CR with GFH009 in a r/r AML patient who had failed all previous lines of therapy, including azacytidine-venetoclax combination, and we were also encouraged that a second patient in the same dosing cohort continued on GFH009 treatment for three months with good health status. These encouraging initial data, with efficacy seen across multiple dose levels, support the potential of GFH009 as a treatment option in AML and lymphoma patients where almost all approved therapies have failed," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "The compelling safety profile even at high dose levels, and significant tumor burden reduction even at low levels, indicates a therapeutic window and combination potential of GFH009 in hardest to treat disease states, including solid cancers."

A total of 57 patients have been enrolled to date, including 31 with r/r lymphoma and 26 with r/r AML. All enrolled patients to date were heavily pretreated with up to six lines of previous therapy. The dose escalating trial was originally planned at fixed per patient doses ranging from 2.5 mg to 30 mg, administered as 30-minute infusions twice a week. The initial design was based on expected toxicities observed in previously published trials with other CDK9 inhibitors, which were primarily severe neutropenias. However, the lack of observed severe toxicities, even at the highest dose level of 30 mg, provided the opportunity to both further escalate the dose levels, and to explore a more patient friendly once a week dosing regimen without sacrificing efficacy. New dosing regimens added to the ongoing trial include 40 mg administered twice per week and 30 mg, 45 mg and 60 mg administered once a week, all of which have been fully enrolled except for the 60 mg cohort. All initially planned dose escalation cohorts with 2.5 mg, 4.5 mg, 9 mg, 15 mg, 22.5 mg and 30 mg of GFH009 administered twice per week are also fully enrolled. The 45 mg once a week cohort, although fully enrolled, has not yet been analyzed.

Apparent efficacy was noted without significant toxicities at multiple dose levels ranging from 9 mg to 30 mg, suggesting a broad therapeutic window, which is a key trait for high combination potential. Stable disease (SD) was maintained in certain patients for more than 8 months and one patient still on treatment has maintained SD for more than a year, which suggests a favorable safety profile with potential for prolonged treatment.

Selective Preliminary GFH009 Monotherapy Efficacy Data in r/r AML Group:

One patient has a confirmed CR and is MRD negative after failing azacytidine–venetoclax regimen
One patient continued on treatment for 3 months
Two patients had blast count decreases of ≥50% in bone marrow (both r/r on azacytidine- venetoclax treatment)
Selective Preliminary GFH009 Monotherapy Efficacy Data in r/r Lymphoma Group:

2 patients had partial response (PR)
4 patients achieved SD with one of them maintaining SD for over a year while still continuing GFH009 monotherapy
The pharmacokinetics (PK) profile of GFH009 shows dose proportional concentrations with a biphasic profile of rapid initial tissue distribution followed by slower elimination from tissues. There were no apparent time-dependent changes in volume of distribution or clearance.

Initial pharmacodynamics (PD) studies have shown clear reductions in two known biomarkers of CDK9 activity, MCL‐1 and MYC. Biomarker response was observed in 97.6% of analyzed patients (41 of 42 patients) with a decrease for either MCL-1 or MYC expression and 95.2% (40 of 42 patients) had a decrease in both biomarkers.

On December 13, 2022 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the treatment paradigm for devastating diseases, reported that Daphne Zohar, Founder and Chief Executive Officer, will present at the 41st Annual J.P. Morgan Healthcare Conference on Tuesday, January 10, 2023, at 2:15 p.m. PST / 5:15 p.m. EST. A webcast of the presentation will be available at View Source (Press release, PureTech Health, DEC 13, 2022, View Source [SID1234625223]).

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On December 13, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported preclinical ORIC-533 data demonstrating a potential best-in-class CD73 inhibitor profile for the treatment of multiple myeloma (Press release, ORIC Pharmaceuticals, DEC 13, 2022, View Source [SID1234625220]).

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"ORIC-533 continues to demonstrate strong potency in reducing adenosine generation and thereby overcoming immune suppression and restoring lysis of multiple myeloma cells as a single agent in ex vivo models," said Jacob M. Chacko, MD, chief executive officer. "We look forward to sharing initial clinical data from the ongoing Phase 1b study of ORIC-533 in patients with multiple myeloma in the first half of 2023."

The ASH (Free ASH Whitepaper) presentation focused on ex vivo proof-of-concept studies with CD73 inhibitors using autologous bone marrow samples derived from patients with multiple myeloma.

Key highlights from the presentation include:

Preclinical analyses continue to show ORIC-533 demonstrates a potential best-in-class CD73 inhibitor profile.
ORIC-533 overcame immune suppression and triggered significant lysis of multiple myeloma cells across all dose levels tested and in a dose-responsive manner, in an autologous ex vivo assay using samples derived from bone marrow aspirates from patients with relapsed refractory multiple myeloma.
Together these preclinical data confirm that single agent ORIC-533 inhibits CD73 to potently reduce adenosine generation, overcome immune suppression and restore lysis of multiple myeloma cells and therefore holds potential as a treatment for patients with multiple myeloma.
About ORIC-533

ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73, a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy and immunotherapy-based treatment regimens. ORIC-533 has demonstrated greater potency in preclinical studies compared to an antibody approach, as well as other small molecule inhibitors of CD73 and adenosine receptor antagonists. Preclinical data demonstrated that ORIC-533 binds CD73 with high affinity and effectively blocks adenosine-driven immunosuppression in a high AMP environment, reflective of AMP levels observed in tumors. In preclinical studies, nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, as well as in ex vivo bone marrow aspirates from relapsed or refractory multiple myeloma patients. A Phase 1b trial with ORIC-533 as a single agent in multiple myeloma is enrolling patients, and the company expects to report initial Phase 1b data from this trial in the first half of 2023.