On April 27, 2020 Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL) reported that it will report its first quarter 2020 financial results after market close on Tuesday, May 5, 2020 (Press release, Rigel, APR 27, 2020, View Source [SID1234556659]). Rigel senior management will follow the announcement with a live conference call and webcast at 4:30pm Eastern Time (1:30pm Pacific Time) to discuss the financial results and give an update on the business.

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Participants can access the live conference call by dialing (877) 407-3088 (domestic) or (201) 389-0927 (international). The conference call and accompanying slides will also be webcast live and can be accessed from the Investor Relations section of the company’s website at www.rigel.com. The webcast will be archived and available for replay for 90 days after the call via the Rigel website.

On April 27, 2020 Actym Therapeutics, a privately-held immuno-oncology company, reported the completion of a $34 million series A financing led by Boehringer Ingelheim Venture Fund (BIVF) and Panacea Venture, with participation from Illumina Ventures, Korea Investment Partners (KIP), and JLo Ventures (Press release, Actym Therapeutics, APR 27, 2020, View Source [SID1234556658]). The company will use the proceeds to advance development of immunotherapies from its microbial-based STACT platform into the clinic for the treatment of various cancers. Actym is led by industry veterans Christopher Thanos, Ph.D., Chief Executive Officer, Laura Hix Glickman, Ph.D., Vice President Research, and Mark Frohlich, M.D., Chief Medical Advisor.

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With the close of the Series A financing, the Actym Board of Directors has expanded to include Kanad Das, Ph.D., Investment Director at BIVF, James Huang, MBA, Founding Managing Partner of Panacea Venture, and Alexis Ji, Ph.D., Partner at Illumina Ventures.

"Patients burdened with metastatic disease desperately need new and effective treatment options. Actym’s platform technology allows for the delivery of multiplexed immunological payloads to the tumor microenvironment (TME) after IV dosing, in a single therapeutic composition. This financing, from an esteemed group of investors, is a key validation of our approach," said Dr. Thanos. "Our goal is to bring therapeutic benefit to cancer patients. We are fortunate to be aligned with investors who can provide both the financial resources and real-world leadership experience to help build Actym, advance our pipeline, and ultimately help patients."

"On behalf of BIVF, we are excited to co-lead the investment in Actym. Actym’s unique approach has the potential to overcome the immunosuppressive TME and treat a broad range of malignancies via a systemic route of administration." said Dr. Das, of BIVF.

"Actym has developed a highly differentiated therapeutic platform. We are excited about its potential and are impressed by the scientific depth of the team. We are thrilled to co-lead the investor syndicate and our team looks forward to helping Actym develop potent immunotherapies." said Mr. Huang.

On April 27, 2020 Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company developing a new class of potent and selective precision oncology medicines, which it refers to as Pentarin miniature drug conjugates, reported that new pharmacokinetic and target engagement data from its Phase 1 study of PEN-866 in patients with solid tumor malignancies at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting (Press release, Tarveda Therapeutics, APR 27, 2020, View Source [SID1234556654]). PEN-866 is the initial clinical program from Tarveda’s HSP90 binding miniature drug conjugate platform, and is designed to bind to activated Heat Shock Protein 90 (HSP90) to accumulate and release its potent topoisomerase 1 inhibitor (SN-38) payload in solid tumors. The poster titled, "Characterization of PEN-866, a Heat Shock Protein 90 (HSP90) binding conjugate of SN-38, in patient plasma and tumors from the first in human study", showcased confirmatory pharmacokinetics of PEN-866 in patient plasma and highlighted data from two patient biopsies, which confirmed higher concentrated levels of the PEN-866 conjugate and SN-38 payload in tumor relative to plasma.

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"The plasma pharmacokinetic data from the dose escalation portion of our Phase 1/2a clinical trial demonstrated that PEN-866 exhibited favorable plasma pharmacokinetics as predicted from our preclinical data, with PEN-866 remaining intact while in circulation. Unconjugated SN-38 remained very low at approximately 2% of the PEN-866 exposure in circulation," said Mark Bilodeau, Ph.D., Chief Scientific Officer of Tarveda. "We are also very encouraged by the tumor biopsy data, which showed tumor uptake and retention of PEN-866 as well as the subsequent release of SN-38, which was significantly increased in comparison to the presence of PEN-866 and released SN-38 in plasma at days 1 and 7/8 after dosing. These data are consistent with PEN-866 preclinical data showing materially increased uptake and retention of PEN-866 in the tumor versus untargeted forms of SN-38, such as irinotecan."

Dr. Bilodeau continued, "the preferential tumor targeting and release of SN-38 seen in the tumors with PEN-866 serves as a firm foundation for the broader potential of the platform to produce new HSP90 binding miniature drug conjugates with promising anti-cancer payloads."

"The clinical and preclinical results seen to date show that PEN-866 accumulates and is retained in tumors where it is then released over multiple days at therapeutic levels. This is in contrast to plasma where the conjugate remains intact and is quickly cleared from the circulation, helping to spare potential damage to normal tissue," said Jeffrey Bloss, M.D., Chief Medical Officer of Tarveda. "These data support the miniature conjugate design of PEN-866 and are a contributor to the beneficial therapeutic index seen with PEN-866 in Phase 1. We are excited to work with PEN-866 in Phase 2a and believe its development should be explored as a single agent and in combination with other exciting therapeutics, such as PARP inhibitors and immuno-oncology drugs that have struggled to successfully combine with cytotoxic therapies."

PEN-866 Phase 1 Study Design & Results

Thirty patients with advanced solid tumor malignancies were enrolled in the Phase 1 dose escalation cohorts and received PEN-866 on days 1, 8, and 15 in 28-day cycles over a dose range of 16-228 mg/m2. The PEN-866 plasma concentration profile showed a concentration decline after end of infusion resulting in an average half-life of approximately 7 hours. PEN-866 plasma concentrations up to 39 µg/mL and area under the concentration curve of 57 h·µg/mL were achieved and determined for the recommended Phase 2a dose. Of the 30 patients, two consented to tumor biopsy collection to determine PEN-866 and SN-38 accumulation. Biopsy results from a pancreatic cancer patient who received a 150 mg/m2 dose of PEN-866 showed that PEN-866 and SN-38 levels in the tumor were significantly higher than observed in plasma 24 hours post dose and that the ratio of SN-38 to PEN-866 was high in tumor and low in plasma. Results from a patient with esophageal cancer who received a 175 mg/m2 dose of PEN-866 on day one and underwent tumor biopsy on day seven showed continued exposure of PEN-866 and SN-38 in the tumor. While in the plasma, PEN-866 was extremely low and SN-38 was unmeasurable (on day 8). These biopsy results support previous preclinical data showing that PEN-866 slowly releases its SN-38 payload in the tumor over multiple days.

Overall the data show that PEN-866 demonstrated favorable plasma pharmacokinetics with low levels of SN-38 observed in plasma. More importantly, both the conjugate and released payload (SN-38) were concentrated and retained in the tumor for up to a week. PEN-866 recently completed the Phase 1 all-comers, dose escalation and safety portion of a Phase 1/2a clinical trial. Additional information on the Phase 1/2a clinical trial for PEN-866 is available at clinicaltrials.gov, through identifier number NCT03221400.

On April 27, 2020 NOXXON Pharma N.V. (Paris:ALNOX) (Euronext Growth Paris: ALNOX), a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported the presentation of the latest clinical results from the Phase 1/2 study with CXCL12 inhibitor, NOX-A12, and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting 2020 (Press release, NOXXON, APR 27, 2020, View Source [SID1234556652]). The data were presented in a short video with commentary by the first author, Dr. Niels Halama, from the National Center for Tumor Diseases (NCT) in Heidelberg, Germany.

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The data indicate that treatment with NOX-A12 plus pembrolizumab in the combination therapy part of the study resulted in stable disease in 25% of patients and prolonged time on treatment vs. prior therapy for 35% of patients. The safety profile of the combination therapy was consistent with that of pembrolizumab in advanced cancer patients. Comparison of tumor biopsies from before and after NOX-A12 monotherapy showed a trend towards agglomeration of T cells within tumors in about half of the patients where NOX-A12 had induced a Th1-type cytokine response. This agglomeration was accompanied by reduced distances between T cells and cancer cells, suggesting increased infiltration of effector immune cells into tumor tissue and a more effective immune response.

"Based on the fact that these indications have so far remained unaffected by checkpoint inhibitors, the outcome of this trial emphasizes the real potential NOX-A12 has on targeting the tumor microenvironment and enabling the intended mode of action of pembrolizumab," said Aram Mangasarian, CEO of NOXXON. "These results provide a strong rationale for moving this program forward into a larger scale randomized trial with a less-advanced patient population, an opportunity we intend to pursue with a partner."

"As a clinician who has worked with colorectal and pancreatic cancer patients, the data provide signals that support the potential impact of the combination of NOX-A12 with pembrolizumab, which is a significant step for these cancers with extremely limited options," commented Dr. Jarl Ulf Jungnelius, CMO of NOXXON.

Access to AACR (Free AACR Whitepaper) Virtual Annual Meeting 2020 is freely available upon registration. NOXXON’s abstract and a short video with commentary (presentation CT117) are now available online in the Virtual Poster Session section VPO.CT01 on the AACR (Free AACR Whitepaper) website, as well as on the NOXXON website.

On Aprii 27, 2020 RGENIX, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, reported it is presenting an abstract on RGX-104, RGENIX’s lead therapy in development. RGENIX’s abstract, "RGX-104, a first-in-class immunotherapy targeting the liver-X receptor (LXR); Initial results from the phase 1b RGX-104 plus Docetaxel combination dose escalation cohorts" was accepted for the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which this year was scheduled as two virtual meetings (Press release, Rgenix, APR 27, 2020, View Source [SID1234556651]). The abstract results will be presented as a virtual poster presentation (CT-146) during the VPO.CT01 – Phase I Clinical Trials session on April 27, by clinical investigator Dr. Emerson Lim from Columbia University Herbert Irving Comprehensive Cancer Center, who is lead author on the study.

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For the dose escalation stage of this Phase 1b study, RGX-104 was tested in combination with docetaxel across three different dose escalation cohorts. The presentation will outline the safety profile, pharmacodynamic effects, and clinical activity of the combination in unselected heavily pre-treated patients with refractory or relapsed solid tumors. The results support further development of this regimen.

RGX-104 is a small-molecule LXR agonist that modulates innate immunity via transcriptional activation of the ApoE gene. RGX-104 inhibits tumor angiogenesis and depletes myeloid derived suppressor cells (MDSC), thereby activating cytotoxic T-lymphocytes. MDSCs are associated with resistance to both checkpoint inhibitors (CPI) and chemotherapy, including docetaxel, providing a rationale for combination therapy with RGX-104. Consistent with this, RGX-104 plus docetaxel combination therapy is highly efficacious in pre-clinical models that demonstrate MDSC-associated docetaxel resistance.

As of February 7, 2020, 11 patients with refractory solid tumors were treated with the combination across 3 different dosing cohorts. The safety profile was consistent with the individual profiles of RGX-104 and docetaxel, with neutropenia the most common drug-related adverse event observed, but dose-limiting in only one patient in cohort one, where RGX-104 was administered at 80mg BID every day with docetaxel administered at 35mg/m2 weekly x 3. In cohorts two and three, in which patients received RGX-104 dosing five consecutive days out of seven (at either 80mg or 100mg BID) and a reduced dose of docetaxel (28mg/m2), no dose-limiting toxicity was observed, and sustained pharmacodynamic activity (ApoE activation and MDSC depletion) was achieved. The overall response rate (ORR) in all evaluable patients was 22%, with a disease control rate (DCR) of 56%. Across cohorts 2 and 3, where target RGX-104 pharmacodynamic effects were achieved, the ORR was 33% with a 67% DCR. Clinical responses included partial responses (PRs) in CPI refractory/resistant patients, including an ongoing confirmed PR in a CPI resistant melanoma patient treated in cohort 2 that remains on study at 10 months. Clinical activity was associated with increases in T cell activation markers exceeding that generally observed with RGX-104 alone.

As a result, the RGX-104/docetaxel regimen is being evaluated in a phase 1b/2 expansion study that has begun enrolling patients with relapsed/refractory extensive stage small-cell lung cancer (ES-SCLC) or high grade-neuroendocrine tumors (HG-NET).

Emerson Lim, M.D., principal investigator from Columbia University Herbert Irving Comprehensive Cancer Center and lead author and presenter of the poster, said, "The clinical activity seen in the dose escalation of RGX-104 combined with Docetaxel is quite encouraging; especially notable is the ongoing PR of greater than 10 months duration in a patient with metastatic melanoma who had previously progressed with combination Nivolumab and Ipilimumab as his second line therapy. I am hopeful this combination will provide a therapeutic option for patients with ES-SCLC/HG-NET as currently being tested in the expansion phase."

RGX-104 is also being evaluated in combination with the front-line standard-of-care regimen of pembrolizumab plus carboplatin/pemetrexed in a phase 1b/2 study currently enrolling patients with advanced non-squamous non-small cell lung cancer (NSCLC).

Masoud Tavazoie, M.D., Ph.D., and Chief Executive Officer of RGENIX, said, "The data from the RGX-104/docetaxel combination dose escalation cohorts are encouraging, providing early safety and efficacy data that support further development of the combination. Though we are still in the early stages of the RGX-104 Phase 1b/2 studies, the results show the potential of RGX-104 to provide durable clinical activity in refractory patients through a novel mechanism-of-action. We look forward to sharing additional findings from these ongoing studies."