On April 20, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that it will release its first quarter 2023 financial results and operational highlights before open of U.S. markets on Thursday, May 4, 2023 (Press release, Autolus, APR 20, 2023, View Source [SID1234630361]).

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Management will host a conference call and webcast at 8:30 am ET/1:30 pm GMT to discuss the company’s financial results and provide a general business update. Conference call participants should pre-register using this link to receive the dial-in numbers and a personal PIN, which are required to access the conference call.

A simultaneous audio webcast and replay will be accessible on the events section of Autolus’ website.

On April 20, 2023 TriSalus Life Sciences Inc., ("TriSalus" or the "Company"), an oncology company in the process of going public through a business combination transaction (the "Business Combination") with MedTech Acquisition Corporation (Nasdaq: MTAC) ("MedTech" or "MTAC"), reported new Phase 1 clinical data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") 2023 Annual Meeting taking place in Orlando, Florida, from April 14-19, 2023 (Press release, TriSalus Life Sciences, APR 20, 2023, View Source [SID1234630359]).

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The clinical data presented at the AACR (Free AACR Whitepaper) 2023 Annual Meeting relates to the Company’s ongoing Pressure-Enabled Regional Immuno-Oncology ("PERIO-01") clinical study for uveal melanoma with liver metastases ("UMLM"). The PERIO-01 trial is studying an investigational class C toll-like receptor-9 agonist, SD-101, delivered intravascularly with the TriNav Infusion System ("TriNav") using the Pressure-Enabled Drug Delivery ("PEDD") method of administration. PERIO-01 is evaluating whether this platform approach can improve the performance of systemic checkpoint inhibitors in patients with UMLM.

PERIO-01 is an open-label, first-in-human Phase 1 trial of SD-101, given by hepatic arterial infusion with TriNav using PEDD in UMLM (NCT04935229). The study consists of dose-escalation cohorts of SD-101 (2, 4, or 8 mg) alone or with immune checkpoint inhibition ("ICI"). At data cutoff as of January 14, 2023, based on pooled data from 27 patients enrolled in the PERIO-01 trial, only 3 patients were treatment naïve, and others received 1-7 lines of prior therapy. Within these 27 patients, there has been one treatment-related serious adverse event. The most common treatment related adverse events overall were fatigue (9 events), abdominal discomfort (6 events), and dizziness (3 events) which were all graded as non-serious. Grade 3 liver function test elevations were noted in one subject, which was not clinically serious.

Circulating tumor cell and circulating tumor DNA ("ctDNA") levels were noted to decrease in 6 out of 13 patients and 6 out of 9 patients, respectively, based on available data. Decreases of ctDNA have been associated with longer overall survival in the stage IV uveal melanoma population. 5 out of 5 patients with available data demonstrated reductions in intratumoral myeloid derived suppressor cells ("MDSCs"), which the Company has previously demonstrated in pre-clinical liver metastasis models to be associated with immunosuppression. This data supports the hypothesis that checkpoint inhibitors in combination with SD-101 delivered via the PEDD method can enable broad immune effects, including the depletion of liver MDSCs.

"We believe our approach has the potential to improve outcomes and enhance the quality of life for patients with liver and pancreatic tumors receiving checkpoint inhibitor therapy," said Steven C. Katz, MD, FACS, Chief Medical Officer at TriSalus. "The data presented at the AACR (Free AACR Whitepaper) 2023 Annual Meeting shows that SD-101 has been well tolerated to date when administered via PEDD, at multiple dose levels alone and in combination with checkpoint inhibition. SD-101 infusions have also been associated with encouraging immunologic activity and ctDNA decreases, even at the lower doses, in heavily pre-treated patients. The serious adverse event rate related to treatment to date suggests that our delivery approach may enhance the therapeutic index for SD-101. We look forward to continuing our trials and adding to the growing body of evidence that our proprietary PEDD method is a potentially powerful approach for enabling SD-101 to improve efficacy of systemic immunotherapies like checkpoint inhibitors."

On April 20, 2023, TRACON Pharmaceuticals, Inc. (the "Company") reported to have entered into a third amendment with effect from April 15, 2023 (the "Loan Amendment") to the loan and security agreement, dated as of September 2, 2022 and amended as of December 22, 2022 and March 31, 2023 (the "RGC Loan Agreement"), by and among the Company, each party to the RGC Loan Agreement from time to time a borrower thereunder, the lenders from time to time a party thereto and Runway Growth Finance Corp., as administrative agent and collateral agent for the lenders ("Lender") (Filing, 8-K, Tracon Pharmaceuticals, APR 20, 2023, View Source [SID1234630358]). The Loan Amendment amends the RGC Loan Agreement to, among other things, provide for the following terms: on or before April 28, 2023, if the Company has raised at least $25.0 million in net cash proceeds from certain equity or debt transactions prior to making such request, Lender may, in its sole and absolute discretion, allow or deny loaning to the Company an aggregate principal amount of $10.0 million, with the full amount funded in a single disbursement. If the loan described above is not made by April 28, 2023, the maturity date will be April 28, 2023, the RGC Loan Agreement will terminate on that date, and the Company will not be obligated to pay the prepayment fee described in the RGC Loan Agreement but the final payment fee described in the RGC Loan Agreement will become immediately due and payable.

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All other material terms, including the interest-only period and covenants in the RGC Loan Agreement, remain unchanged.

The foregoing summary of the material terms of the Loan Amendment does not purport to be complete and is subject to, and qualified in its entirety by, the full text of the Loan Amendment, a copy of which will be filed with the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2023.

On April 20, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for SNS-101, a conditionally active VISTA-blocking antibody, paving the way for the Company to conduct a Phase 1/2 clinical trial in patients with solid tumors (Press release, Sensei Biotherapeutics, APR 20, 2023, View Source [SID1234630357]).

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"Receiving IND clearance to advance our first conditionally active antibody into a Phase 1/2 clinical trial represents an important milestone for Sensei. We believe that SNS-101 has the potential to make a significant impact in the field and to improve the lives of cancer patients worldwide," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "We are delighted to bring SNS-101 into the clinic and explore its potential as a transformative treatment option for patients with solid tumors."

The Phase 1/2 clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101 as both a monotherapy and in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab) in solid-tumor cancer patients. The Phase 1 dose escalation portion of the clinical trial will be followed by an expansion Phase 2 in selected patient populations once a recommended Phase 2 dose is determined. SNS-101 will be administered as an intravenous infusion once every three weeks. Sensei expects to dose the first patient in mid-2023.

"Based on our preclinical data, we believe SNS-101 will be the first antibody to meaningfully explore the VISTA axis in the immuno-oncology space, with potential to achieve a higher therapeutic index and a more favorable tolerability profile than drugs limited by toxicity and poor pharmacokinetics," said Edward van der Horst, Ph.D., Chief Scientific Officer of Sensei.

SNS-101 is a conditionally active, human monoclonal IgG1 antibody designed to selectively block the VISTA checkpoint in the tumor microenvironment, which acts as a suppressor of T cells by binding the receptor PSGL-1. Preclinical studies have demonstrated SNS-101’s potential to inhibit tumor growth as monotherapy, significantly enhance the anti-tumor effects of PD-1 blockade, avoid poor pharmacokinetics from target-mediated drug disposition and lower the risk of cytokine release syndrome.

On April 20, 2023 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported completion of the safety evaluation stage of the highest dose cohort of patients with acute myeloid leukemia (AML) who relapsed after or were refractory to available antileukemic therapies in its Phase 1 dose escalation clinical trial of GFH009 (Press release, Sellas Life Sciences, APR 20, 2023, View Source [SID1234630356]). No further dose escalations are planned in the AML group, while dose escalation continues in the lymphoma group with the addition of a 75 mg once-a-week dose cohort, which is planned to be the highest dose level for that group.

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"We are very encouraged by the strong efficacy signals and safety profile of our highly selective CDK9 inhibitor, GFH009, observed in this positive Phase 1 trial. We believe GFH009 could have the potential to address a major unmet medical need of patients with AML who relapse following treatment," said Angelos Stergiou, M.D., Sc.D. h.c., President and CEO of SELLAS. "We are highly motivated to expedite advancement of GFH009 with our upcoming Phase 2a trial, in order to potentially bring this novel treatment to AML patients who need it as quickly as possible."

"I am very much looking forward to participation in the Phase 2a clinical trial of GFH009," said M. Yair Levy, MD, the Director of Hematologic Malignancies research at Texas Oncology Baylor Charles A. Simmons Cancer Center in Dallas, TX. "Although venetoclax is a backbone of many AML treatments, some patients do not respond to treatment and many relapse after initial response. CDK9 inhibition in general, and GFH009 in particular with the AML data seen thus far, has a strong biological basis of synergy with the BCL2 inhibitor venetoclax and we hope that it may overcome leukemic cell resistance in the upcoming trial, given that it appears that MCL-1 upregulation plays a key role in developing venetoclax resistance and we have seen in the Phase 1 trial that GFH009 decreases MCL-1 levels."

The Company is finalizing the comprehensive data analysis to determine the recommended Phase 2 dose (RP2D) in AML, which will be announced following review by the U.S. Food and Drug Administration (FDA). SELLAS plans to commence a Phase 2a clinical trial during the second quarter of 2023 with GFH009 in combination with venetoclax and azacitidine (aza/ven) in patients with AML who relapsed after or are refractory to treatment with venetoclax based therapies. The trial will be a single arm open label dose ranging study with one dose level at the RP2D and one dose below RP2D. Primary endpoints will be complete response composite (CRc) rate and safety, and secondary endpoints will include duration of response (DOR), event free survival (EFS), overall survival (OS) and proportion of patients proceeding to transplant. The trial will include several sites in the United States, will initially enroll approximately 20 patients and, based on initial results, may be expanded into a registrational trial. Topline data from this study are expected in the fourth quarter of 2023.

Phase 1 results from the AML group :

In the Phase 1 trial, the AML group included dose levels of 9 mg, 15 mg, 22.5 mg, 30 mg, 40 mg, 45 mg and 60 mg. Dose levels of 9 mg to 40 mg were administered two times per week and dose levels of 30 mg, 45 mg and 60 mg were administered once a week.

Anti-tumor activity has been observed in both the AML and lymphoma groups in the Phase 1 trial at multiple dose levels, including a complete response, partial responses, stable disease, and decreases in tumor burden. GFH009 continued to be safe and well tolerated at all dose levels, with no dose limiting toxicities and no significant off target toxicities observed. Due to the encouraging safety profile, the maximum tolerated dose level has not been reached.

In the AML group, no further dose escalation is planned as all Phase 1 trial objectives in AML have been successfully met and results are summarized below:

Clinical efficacy was demonstrated with a complete response achieved at an intermediate dose level
Biological efficacy was observed with 50% or more decrease in leukemic cell blasts in bone marrow at multiple dose levels and 75% bone marrow blasts decrease at the highest studied dose level
Pharmacokinetics above IC90 in peripheral blood was maintained for 24 hours at target dose level
IC90 plus concentrations in peripheral blood were achieved after first infusion with once-a-week administration at the highest studied dose level
Pharmacodynamics representing consistent and dose related decrease in MCL1 and MYC biomarkers expression
Phase 2a trial in combination with aza/ven in patients with AML :

Disease relapse in patients with AML after initial response to aza/ven is a major unmet medical need with median overall survival of only 2.5 months. While the aza/ven regimen is a backbone of AML treatment, approximately one-third of patients do not respond to treatment and almost all patients who initially respond eventually relapse.

Based on the available Phase 1 data, the Phase 2a trial design will be submitted to the FDA by the end of the month. GFH009 will be studied in the Phase 2a trial in combination with aza/ven in patients relapsed after or refractory to venetoclax based therapies and will be based on the parameters discussed with the FDA. The study regimen is designed based on clinical data that showed efficacy in patients relapsing after aza/ven induced complete responses, preclinical in vivo data that demonstrated high levels of synergy of GFH009 and venetoclax in mouse models of AML, and in vitro biological synergies between BCL2 and MCL1 inhibition and AML cells dependence on MCL1 and BCL2. In addition, a significant proportion of patients with AML exhibit MYC dependence.