On April 8, 2022 Applied Pharmaceutical Science reported that disclosed for the first time the critical preclinical data of the next-generation RET inhibitor APS03118 at AACR (Free AACR Whitepaper) 2022 annual meeting (Press release, Applied Pharmaceutical Science, APR 8, 2022, View Source [SID1234613105]). The data shows that APS03118 is a highly selective next-generation RET inhibitor that strongly inhibits multiple RET aberrances in vitro and in vivo, and can be used in patients with acquired resistance to the first-generation RET inhibitors.

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APS03118 is an innovative drug developed by APS for unlimited cancers with global independent intellectual property rights. Potential indications include non-small cell lung cancer(NSCLC), thyroid cancer, breast cancer, colorectal cancer and other metastatic solid tumors with RET aberrances.

RET aberrances contain fusions and mutations that lead to over-activation of RET signaling pathways and uncontrolled cell growth. As RET oncogene is present in a variety of cancers，it has become an important target of "unlimited cancer" therapies. Tumors with RET alterations primarily rely on abnormal activation of this kinase to promote proliferation and growth, therefore RET positive tumors are sensitive to RET inhibitors.

Although RET oncogene is closely related to various of cancers, only selpercatinib and pralsetinib were approved recently as the selective RET inhibitors. Selective RET inhibitors are effective in RET positive patients but followed by acquired drug resistance and progress disease. On-target resistances include the acquisition of solvent front mutations (SFMs) RET G810 R/S/C that have been identified as a predominant mechanism to both selpercatinib and pralsetinib. The roof RET L730I/M, gate keeper RET V804M/L/E, and hinge RET Y806 mutations are also important resistance mutations to current MKI and selective RET inhibitors. Therefore, a next-generation RET inhibitor should potently against SFMs and a broad range of other mutations.

APS03118 is the highly selective and potent next-generation RET inhibitor

• APS03118 was highly selective against a panel of 468 kinases at 100 nM compound concentration (performed at Eurofins).

• No concerning off-target finding in Eurofins Safety47 panel at the 10 μM compound concentration.

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APS03118 is potent against RET alterations in vitro

• APS03118 is potent against wild-type (WT) and a board range of mutant RET in comparison with selpercatinib and pralsetinib in the enzymatic and cell-based assays, especially the SFMs RET G810 R/S/C, gate keeper RET V804M/L/E, roof RET L730I/M and hinge RET Y806 mutations that induced the resistance to RET inhibitors.

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APS03118 shows potent antitumor efficacy in xenograft mouse tumor models

• APS03118 is highly active in xenograft tumor models including KIF5B-RET PDX, KIF5B-RET V804M CDX and KIF5B-RET G810R CDX models.

• Tumors completely subsided in orthotopic brain PDX model harboring CCDC6-RET with a 100% survival rate in APS03118 treated group.

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RET is closely related to the occurrence of a variety of human tumors. Lung cancer is the malignant tumor with the highest morbidity and mortality in China, and NSCLC is the most common type of lung cancer. NSCLC patients with RET gene alterations are not uncommon in clinic. In addition, the incidence of brain metastasis is high in lung cancer patients, which is closely related to the positive RET fusion with the cumulative incidence of more than 60% in 24 months. APS03118 may provide a better therapeutic option for NSCLC and thyroid cancer induced by RET aberrances.

Dr. Jun Zhong, vice president of R&D of APS, stated: "APS03118 has proved its great potential in the treatment of cancers with RET aberrances in preclinical studies. By participating the AACR (Free AACR Whitepaper) meeting, We hope the RET-targeted therapy would attract more attention, and provide optimized options for the patients with acquired resistance to the first-generation selective RET inhibitors in response to the global unmet medical needs in this field."

Investigational New Drug (IND) application of APS03118 was approved by FDA early this year, and APS03118 was also granted the Fast Track Designation by FDA. APS03118 released key preclinical data on AACR (Free AACR Whitepaper) meeting would add more confidence to ongoing global clinical trial.

On April 8, 2022 AnPac Bio-Medical Science Co., Ltd. ("AnPac Bio," the "Company" or "we") (ANPC), a biotechnology company with operations in the United States and China focused on early cancer screening and detection, reported that Dr. Aidong Chen has joined the Company as its board director, Chief Executive Officer and Chairman of the Board of Directors (Press release, Anpac Bio, APR 8, 2022, View Source [SID1234611966]). Dr. Aidong Chen has been a practicing physician and researcher for over 10 years. He has received over 20 global patents on his work and published 91 papers over his career. Dr. Chen has been affiliated with many leading hospitals, including Yijishan Hospital, and Nanjing Medical University. He has replaced Dr. Chris Yu, Company’s founder, who resigned as board director, CEO and Chairman of the Board of the Company. As head of China operations of the Company, Dr. Yu will remain with the Company in a senior management role to focus on growing business in China.

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The Company will also be adding Sheng "Dorothy" Liu to the Board of Directors, who will be replacing Mr. Chao Feng. Ms. Liu is currently the CEO of Zhongjintai Venture Capital (Shenzhen) Co., Ltd., a venture capital firm in Shenzhen. She has worked in finance and consulting, including in private equity, for almost ten years. Ms. Liu will be an independent director and will also serve as a member of the Compensation Committee and Chairperson of the Nominating Committee.

On April 8, 2022, Vyant Bio, Inc. (the "Company") reported that entered into an Equity Distribution Agreement (the "Sales Agreement") with Canaccord Genuity LLC (the "Agent"), pursuant to which the Company may issue and sell, from time to time, shares of its common stock having an aggregate offering price of up to $20,000,000 (the "Shares"), depending on market demand, with the Agent acting as an agent for sales (Filing, 8-K, Cancer Genetics, APR 8, 2022, View Source [SID1234611927]). Sales of the Shares may be made by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415(a)(4) of the Securities Act of 1933, as amended (the "Securities Act"), including, without limitation, sales made directly on or through the NASDAQ Capital Market . The Agent will use its commercially reasonable efforts to sell the Shares requested by the Company to be sold on its behalf, consistent with the Agent’s normal trading and sales practices, under the terms and subject to the conditions set forth in the Sales Agreement. The Company has no obligation to sell any of the Shares. The Company may instruct the Agent not to sell the Shares if the sales cannot be effected at or above the price designated by the Company from time to time and the Company may at any time suspend sales pursuant to the Sales Agreement.

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The Company will pay the Agent a commission of up to 3.0% of the gross proceeds from the sale of Shares by the Agent under the Sales Agreement. The Company has also agreed to reimburse the Agent for its reasonable documented out-of-pocket expenses, including fees and disbursements of its counsel, in the amount of $75,000. In addition, the Company has agreed to provide customary indemnification rights to the Agent.

The Offering will terminate upon the earlier of (i) the issuance and sale of all Shares subject to the Sales Agreement, or (ii) the termination of the Sales Agreement as permitted therein, including by either party at any time without liability of any party.

Any sales of Shares under the Sales Agreement will be made pursuant to the Company’s Registration Statement on Form S-3 (File No. 333-239497), including the related prospectus, filed with the Securities and Exchange Commission (the "SEC") on June 26, 2020 and declared effective on July 21, 2020, as supplemented by the prospectus supplement dated April 8, 2022, and any applicable additional prospectus supplements related to the Offering that form a part of the Registration Statement, for an aggregate offering price of up to $20,000,000. The aggregate market value of Shares eligible for sale in the Offering and under the Sales Agreement will be subject to the limitations of General Instruction I.B.6 of Form S-3, to the extent required under such instruction. Due to the offering limitations applicable to the Company under General Instruction I.B.6. of Form S-3 and the Company’s public float as of April 8, 2022, and in accordance with the terms of the Sales Agreement, the Company may offer Shares having an aggregate gross sales price of up to $14,500,000 pursuant to the prospectus supplement dated April 8, 2022. The Company intends to use the net proceeds from this offering for general corporate purposes and for working capital.

The foregoing description of the Sales Agreement does not purport to be complete and is qualified in its entirety by reference to the Sales Agreement, which is filed as Exhibit 1.1 to this report and is incorporated herein by reference. A copy of the legal opinion of Lowenstein Sandler LLP regarding the legality of the issuance and sale of the Shares is filed as Exhibit 5.1 to this report and is incorporated by reference herein.

On April 8, 2022 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported the presentation of new preclinical and translational data for SRF388, a first-in-class antibody targeting IL-27, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, being held in New Orleans, April 8-13, 2022 (Press release, Surface Oncology, APR 8, 2022, View Source [SID1234611835]). The data will be presented in a poster session, "Determination of a Recommended Phase 2 Dose (RP2D) for SRF388, a First-in-Class IL-27–Blocking Antibody, in Patients with Advanced Solid Tumors" (Abstract #1137) from 9:00 a.m. – 12:30 p.m. CT on Monday, April 11, 2022.

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"We are very pleased to share the compelling preclinical and translational data that enabled us to select the dose for our Phase 2 trials of SRF388," said Alison O’Neill, M.D., chief medical officer. "These data add to the growing body of evidence supporting our belief that IL-27 is a highly immunosuppressive cytokine that serves as a critical regulator of checkpoint protein expression, and treatment with SRF388 shuts down IL-27 signaling. We look forward to providing a clinical update on the program at a scientific conference later in the first half of 2022."

Summary of key SRF388 data:

Pharmacokinetics (PK) from the dose-escalation phase of the SRF388 Phase 1 study were linear, with no dose-limiting toxicities reported.
The concentration of SRF388 associated with optimal antitumor activity in a preclinical mouse model was determined to be approximately 20-fold above the concentration needed for complete inhibition of whole blood phosphorylated STAT1; this concentration of SRF388 was reached and exceeded in patients at a dose of 10 mg/kg.
As previously reported, one patient with squamous non-small-cell lung cancer experienced a confirmed partial response per RECIST v1.1 at this dose.
Changes in the concentration of several serum cytokines and chemokines were observed after SRF388 treatment, including a subset of these biomarkers that correlated with clinical response.
An increase in serum IL-27 levels was observed after SRF388 treatment, a phenomenon described for other anti-cytokine antibodies due to altered clearance of the cytokine-antibody complex.
SRF388 translational data supports the recommended Phase 2 monotherapy dose selection of 10 mg/kg administered intravenously every four weeks, which is being studied in dedicated expansion cohorts of treatment-refractory clear cell renal cell carcinoma (RCC), non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) in the ongoing Phase 1 study (NCT04374877).
The efficacy of adding IL-27 blockade with SRF388 to atezolizumab/bevacizumab in treatment-naïve HCC is also being explored in a placebo-controlled randomized Phase 2 study.
The AACR (Free AACR Whitepaper) e-poster website will be launched on Friday, April 8, 2022, and posters will remain available to registered attendees through Wednesday, July 13, 2022. The SRF388 poster can also be found on Surface Oncology’s website.

On April 8, 2022 Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, reported preclinical data at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Shattuck Labs, APR 8, 2022, View Source [SID1234611834]). This includes data from SL-9258 (TIGIT-Fc-LIGHT), derived from the company’s ARC platform, and the company’s GADLEN platform.

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"We have made excellent progress advancing compounds in our preclinical pipeline," said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. "Data from our SL-9258 compound indicate potent modulation of myeloid cells, T cells, and cytokines, including IL-2, which collectively translated to superior anti-tumor activity in comparison to TIGIT and PD-L1 antibodies in a preclinical model of PD-1 acquired resistance. In addition, multiple compounds from our gamma delta T cell engager, or GADLEN, platform have shown specific anti-tumor activity in preclinical studies, which will help guide our lead candidate selection and clinical development strategy. We look forward to nominating our next clinical product candidate in 2022."

Details of the presentations are as follows:

Abstract title: LIGHT (TNFSF14) costimulation with TIGIT blockade broadens the activity of checkpoint inhibitors (CPIs) into checkpoint inhibitor refractory and resistant tumors through targeted myeloid cell and effector lymphocyte activation

Shattuck presented preclinical data for SL-9258 (TIGIT-Fc-LIGHT), a bispecific fusion protein from its ARC platform, demonstrating that SL-9258 simultaneously provides checkpoint blockade to all tumor-expressed PVR ligands and broadens immune costimulation by the TNF ligand known as LIGHT. LIGHT’s ability to bind and activate CD8+ T and natural killer cells through interactions with one of its receptors known as HVEM and myeloid cells through interactions with its other receptor known as LTbR, translates into strong anti-tumor responses in checkpoint primary and acquired resistance murine tumor models, where TIGIT blocking antibodies demonstrate no activity.

TIGIT-Fc-LIGHT was evaluated and well tolerated in non-human primates at doses up to 40 mg/kg and similar on-target pharmacodynamic activity was observed to what was characterized preclinically in mice. Together, these results suggest that TIGIT-Fc-LIGHT may provide clinical benefit to patients that are refractory to conventional checkpoint blockade therapy.

Abstract title: Bispecific gamma/delta T cell engagers containing butyrophilin 2A1/3A1 heterodimeric fusion protein efficiently activate Vg9Vd2+ T cells and promote tumor cell killing

Shattuck presented preclinical data highlighting the potential of GADLENs to direct gamma delta T cells to kill tumor cells and in the process, further elucidate tumor cell markers which are important for the therapeutic activity of gamma delta T cell-based therapies.

Shattuck’s bispecific GADLENs containing heterodimeric BTN2A1 and BTN3A1 extracellular domains fused via inert Fc linkers to scFv domains, targeting CD19 or CD20 tumor-antigens, demonstrated an ability to induce proliferation, degranulation, and cytokine production in Vg9Vd2+ T cells with costimulation of a natural cytotoxicity receptor or T cell costimulatory receptor. Further, CD19 and CD20 directed GADLENs enhanced the specific killing of lymphoma cells that express both antigen targets.

Additional meeting information can be found on the AACR (Free AACR Whitepaper) website, View Source The posters will be available under Posters on the Company’s website shortly after the event.