On April 8, 2022 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported preclinical data supporting the potential of its farnesyl transferase inhibitor (FTI) tipifarnib to prevent emergence of resistance to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib in EGFR mutant non-small cell lung cancer (NSCLC) (Press release, Kura Oncology, APR 8, 2022, View Source [SID1234611665]).

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The new findings, generated through a collaboration with INSERM (the French National Institute of Health and Medical Research), are being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans. A copy of the poster, entitled "Tipifarnib prevents emergence of resistance to osimertinib in EGFR mutant NSCLC," is available at www.kuraoncology.com. A copy of the manuscript is also available at www.biorxiv.org while it undergoes scientific peer-review for publication.

Using Rho-pathway inhibitor screening, researchers at INSERM found that tipifarnib induced a complete clearance of drug-tolerant dormant cells, a potential mechanism of resistance to EGFR-targeted therapy in NSCLC. Several farnesylated targets were identified that appear to control the ability of tumor cells to enter and exit a drug-tolerant state. In parallel, using preclinical in vivo models of EGFR-mutated lung tumors, co-treatment with tipifarnib durably prevented relapse to osimertinib for up to six months, with no evidence of toxicity. Collectively, this mechanistic and translational research strongly supports the potential use of a FTI to prevent or delay the adaptive response to osimertinib in patients with EGFR-mutated NSCLC.

"These preclinical data, combined with our own translational research, support the potential use of tipifarnib in combination with osimertinib to effectively and durably prevent relapse to EGFR-targeted therapies," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "We believe these data represent a paradigm shift in how to use FTIs in combination with targeted therapies to drive clinical benefit in large solid tumor indications. In addition to the near-term opportunity to combine FTIs with EGFR inhibitors, we continue to investigate combinations with other targeted therapies in preclinical studies that may represent additional opportunities."

Kura is preparing to initiate a Phase I clinical trial (KURRENT-LUNG) of tipifarnib in combination with osimertinib in treatment-naïve locally advanced/metastatic EGFR mutated NSCLC and expects to dose the first patient in the third quarter of 2022. The Company intends to perform initial clinical evaluation with tipifarnib while in parallel advancing KO-2806, the lead development candidate in its next-generation FTI program, through investigational new drug (IND)-enabling studies. Kura plans to submit an IND application for KO-2806 in the fourth quarter of 2022.

On April 8, 2022 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a clinical stage biotechnology company developing the next generation of therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported positive new preclinical data showing PH-894, a self-delivering RNAi compound targeting the bromodomain-containing protein 4 (BRD4), provides abscopal efficacy toward untreated distal tumors and potentiates the efficacy of systemic anti-PD-1 antibody therapy (Press release, Phio Pharmaceuticals, APR 8, 2022, View Source [SID1234611664]). These new data will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, which is being held in New Orleans, Louisiana, from April 8-13, 2022.

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Data from in vivo studies demonstrated that PH-894 inhibits tumor growth in both PD-1 inhibition responsive, as well as PD-1 inhibition insensitive models. In both models, after local administration, strong antitumor efficacy was seen in directly treated as well as distal, untreated tumors. Additionally, intratumoral treatment with PH-894 enhanced the antitumor efficacy of systemic anti-PD-1 antibody therapy, not only for the PH-894 locally treated tumors, but for the PH-894 untreated distal tumors. In the PD-1 inhibition insensitive model, local PH-894 therapy was shown to be efficacious as a systemic anti-PD-1 antibody treatment, and enhanced the antitumor efficacy of anti-PD-1 treatment when used together.

"We are excited by these new data on PH-894, our second product candidate, for various reasons," said Dr. Simon Fricker, Phio’s VP of Research & Development. "First, these data show that local administration of PH-894 resulted in systemic efficacy, similar to what we have shown with PH-762. In addition, these studies have shown PH-894 to be a potent standalone treatment in a challenging model, while also enhancing the efficacy of systemic anti-PD-1 antibodies. We believe these data provide a strong rationale for the clinical use of PH-894 as a monotherapy, as well as in combination with systemic PD-1 therapy. Considering the novel mechanism of action of PH-894, there is potential for it to play an important role in treating patients who do not respond to anti-PD-1 therapy, or patients who progress after initially responding to such therapy, addressing an important medical unmet need."

Studies were conducted in colon and liver cancer animal models in which the cancer cell lines were implanted subcutaneously into the bilateral flanks of mice. Tumors on only one side were treated with PH-894, and tumors on the opposite side were left untreated. Some of the animals also received systemic anti-PD-1 antibody treatment in addition to local PH-894 administration. These data showed that locally administered PH-894 inhibited tumor growth of both directly-treated and distal tumors in two cancer models. In addition, PH-894 also potentiated the efficacy of a systemic anti-PD-1 antibody toward PH-894 treated and untreated distal tumors. Ex vivo analysis showed that PH-894 silenced BRD4 and its downstream effector PD-L1 in tumor dendritic cells and increased migratory dendritic cells in the tumor, suggesting a mechanism by which local PH-894 treatment confers systemic tumor control.

Phio’s presentation detailing the data presented at AACR (Free AACR Whitepaper) titled, "Local administration of BRD4-targeting self-delivering RNAi (PH-894) provides abscopal efficacy toward untreated distal tumors and potentiates the efficacy of systemic anti-PD-1 antibody therapy" will be made available on the "Investors – Events and Presentations" section of the Company’s website (click here).

On March 8, 2022 Senti Bio, a leading gene circuit company, reported the acceptance of an abstract for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in New Orleans taking place April 8–13, 2022 (Press release, Senti Biosciences, APR 8, 2022, View Source [SID1234611663]).

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The abstract, titled "Driving anti-tumor activity in solid tumors with controlled arming of allogeneic CAR-NK cells," details the Company’s efforts to develop gene circuits to arm chimeric antigen receptor natural killer (CAR-NK) cells with multiple cytokines to improve the cytotoxicity and persistence of its CAR-NK cell product candidates. Specifically, the authors outline the benefits of calibrated release gene circuit technology, which combines the advantages of secreted and membrane-tethered cytokine-mediated stimulation of the patient’s immune system, to better control solid tumors. This technology is being applied in the design of multiple Senti Bio pipeline products including SENTI-301 and SENTI-401, which are aimed to treat solid tumors such as hepatocellular carcinoma (HCC) and colorectal cancer (CRC) respectively.

A major obstacle in treating solid tumors with cell therapies is overcoming the immunosuppressive tumor microenvironment (TME). Senti Bio has designed and optimized gene circuits to arm CAR-NK cells with cytokines, which improve the cells’ cytotoxicity and persistence, potentially enhancing the probability of durable therapeutic efficacy. While secreted cytokines are well known to stimulate the immune system to fight solid tumors, they are often associated with systemic toxicity. Membrane-bound cytokines, by contrast, can cause a more localized and potent stimulation of the CAR-NK cells but have limited impact on the broader tumor microenvironment.

Senti Bio’s calibrated release gene circuit technology results in optimized distribution to take advantage of the best features of both secreted and membrane-tethered cytokines. The authors also show that combining the cytokines interleukin 15 and 21 (IL-15 and IL-21) significantly prolongs the survival and anti-tumor activity of CAR-NK cells. Overall, the results suggest the advantage of multi-arming CAR-NK cells with cytokines, using Senti Bio’s novel calibrated release technology and cytokine combinations, resulting in improved CAR-NK cell function in solid tumor models.

The abstract is available now on the AACR (Free AACR Whitepaper) website, and the full poster presentation will be available on the Senti Bio and AACR (Free AACR Whitepaper) websites starting April 8.

On April 8, 2022 Locust Walk reported that deal team members compile key statistics and trends on strategic transactions and financings (Press release, Locust Walk Partners, APR 8, 2022, View Source;utm_medium=rss&utm_campaign=2022-q1-report [SID1234611662]). Our 2022 First Quarter Report applies the latest data to analyze current activities in the life sciences deal landscape.

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In this report you can find an overview and analysis of the following across the biopharma market in the US, Europe, and Asia (Japan and China):

Key performance indicators for the life science market​
IPO and private financing activity and performance​
Deal activity for strategic partnership and M&A
A look ahead and our predictions of the future
Biopharma Indices Summary

The biopharma indices continued their decline in 2022 against a backdrop of continued macroeconomic and political uncertainty, negative investor sentiment and rotation to more value-driven investments

2H 2021 saw the BTK and NBI underperform relative to the S&P by ~18% and ~10%, respectively
At the conclusion of Q1 2022, the BTK (~-8%) and NBI (~-12%) continued to underperform
While biopharma indices stumbled, the S&P remained relatively steady over the past 12 months and outperformed the BTK and NBI by ~21% and ~26%, respectively
With the highest inflation rate in decades and the likely increase in interest rate from the Federal Reserve, generalist capital is exiting biotech in search of more conservative sectors
With the recent downturn in public markets, biotech investors have begun to shift their public portfolios in favor of later clinical-stage companies with near-term newsflow, and away from earlier-stage preclinical companies which had received much of the attention during the biotech boom of the last 24 months
Increased M&A in 2022 may provide a catalyst for renewed sector interest

Following the record number of biotech IPOs in 2021, many public biotech companies have the cash on hand to pursue M&A with depressed valuations
However, it may take several more months before those valuations reach a level that sparks the anticipated wave of M&A
Locust Walk has seen increased seller interest in exploring strategic options

On April 8, 2022 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported that it will participate in the Canaccord Genuity Horizons in Oncology Conference (Press release, Delcath Systems, APR 8, 2022, View Source [SID1234611661]):

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Date: April 14, 2022 at 3:00 PM ET
Format: Fireside Chat
Webcast link: View Source
Management will be participating in virtual one-on-one meetings throughout the event. To arrange a meeting with management, please contact your conference representative or [email protected].