On November 12, 2021 MingSight Pharmaceuticals reported the close of a pre-Series B round of $20M, led by Kaitai Capital (Press release, MingSight Pharmaceuticals, NOV 12, 2021, View Source [SID1234595475]). The proceeds will be used for the clinical development of MS-553, a new generation inhibitor of protein kinase C (PKC) beta for the treatment of Chronic lymphocytic Leukemia (CLL) and Diabetic Macular Edema (DME).

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"We greatly appreciate the trust and support of our investors," said Kai Zhang, MD, MBA, CEO and Co-founder of MingSight. "This investment will facilitate the rapid development of the MS-553 program. We are very excited to see MS-553 demonstrate strong efficacy and safety data in our CLL and DME trials. We will work hard to bring forward a truly differentiated product to market to improve upon the treatment options for these serious diseases."

Michael Niesman, Ph.D., CSO and Co-founder of MingSight, said: "We are very glad that our investors share our excitement about the promise of MS-553. Many companies have been convinced of the importance of Protein Kinase C (PKC) in serious diseases like CLL and diabetic eye disease. Because of the major innovations of MS-553 compared to previous pan-PKC inhibitors, we have been able to generate data demonstrating proof of mechanism and significant activity in CLL and DME where other PKC inhibitors have failed. We look forward to working with Kaitai and our other investors to accelerate the development of this unique compound."

Zehua Huang, Partner at Kaitai Capital, said: "We believe MingSight has a world class team and advisory group, and its program is well positioned for the future marketplace. With initial efficacy in CLL patients with C481S and PLCG2 mutations, MS-553 showed distinct promise of its market potential. MS-553 has the potential to improve upon the standard of care therapies for CLL as a single agent or in combination with BTK inhibitors, BCL-2 inhibitors, or other agents. As for its application in DME treatment, MS-553 has the potential to provide an alternative, non-invasive approach to ocular injections of anti-VEGF agents. A key characteristic of MS-553 is its preferential distribution to the retina following oral administration. The initial clinical data of MS-553 in DME patients such as BCVA and CRT readings are very impressive. We are confident that MingSight will succeed in rapidly developing MS-553 and bringing its benefits to patients worldwide."

About MS-553

MS-553 is an investigational drug candidate and a new generation PKC beta inhibitor. It differentiates from the previous generation of pan-PKC inhibitors with its novel chemotype and significant advantages in selectivity, safety, and PK properties.

MS-553 is a potentially the only B-cell receptor inhibitor in clinical development that can address the BTK resistant mutations in both BTK and PLCG2. Its mechanism of action is also synergistic or additive to other approaches that constitute the current standard of care of CLL.

MS-553 also has the potential, if approved, to become the first oral DME therapy with anti-VEGF like efficacy. MS-553 has the unique PK property of preferential distribution to the retina and its mechanism of action addresses both the aberrant VEGF signaling and the inflammation that are characteristics of DME.

In a phase 1/2 study, MS-553 demonstrated promising efficacy and safety in CLL patients who have failed BTK inhibitors including those with C481S and PLCG2 resistant mutations. MS-553 also demonstrated clinical activities including reduction of retinal thickness and improvement of visual acuity in a phase 1b trial of DME patients.

On November 12, 2021 Grey Wolf Therapeutics, a biotechnology company spearheading a new therapeutic approach to immuno-oncology driven by targeted neoantigen generation, reported the presentation of promising preclinical in vivo data on the company’s first-in-class inhibitors of ERAP1 at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Grey Wolf Therapeutics, NOV 12, 2021, View Source [SID1234595491]). The results are featured in a poster presentation (#553) entitled, "First-in-Class Inhibitors of ERAP1 Alter the Immunopeptidome of Cancer, Driving a Differentiated T Cell Response Leading to Tumor Growth Inhibition," at the SITC (Free SITC Whitepaper) conference, being held November 10-14, 2021 in Washington, D.C., as well as virtually.

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Grey Wolf Therapeutics’ first-of-its-kind immuno-oncology approach is centered on dramatically increasing the visibility of tumors to allow for their identification and destruction by the body’s immune system. This is achieved through targeted inhibition of the endoplasmic reticulum aminopeptidases (ERAP1 and ERAP2), causing the generation and presentation of novel and potent neoantigens to the surface of tumor cells. The appearance of these neoantigens uncloaks the tumor cells, illuminating them for the immune system and setting in motion powerful, differentiated T cell responses against the tumor. Importantly, this unique approach is orthogonal to a broad range of other cancer therapy modalities, including, but not limited to, immunotherapy.

The presented findings at the SITC (Free SITC Whitepaper) conference provide compelling evidence for several key elements of the company’s therapeutic hypothesis for ERAP1 inhibition in the treatment of cancer. These include the ability of the company’s ERAP1 inhibitors to drive neoantigen creation, differentiated T cell responses, and tumor growth inhibition.

Key highlights from the company’s presentation include:

Neoantigen Creation

Researchers highlighted study results demonstrating that ERAP1 inhibition triggered clear generation of novel neoantigens, as well as increased expression of existing neoantigens, across various species, cell types and genetic backgrounds in vitro and in vivo. For example, targeted ERAP1 inhibition within the HCT116 colorectal cancer cell line led to increased surface expression of key cancer antigens including MAGE3 and PBK, as well as the generation of an entirely new neoantigen (ATAD2) within the tumor. This neoantigen generation is believed to make the tumor significantly more visible to the immune system, allowing for the desired differentiated T cell response.

Differentiated T Cell Response

Presented findings highlighted three different data sets supporting the ability of ERAP1 inhibition to drive a differentiated T cell response.

First, results demonstrated a statistically significant increase in T cell receptor (TCR) diversity across a range of timepoints following treatment with an ERAP1 inhibitor and an anti-PD-1 antibody in the CT26 tumor model. Second, data demonstrated that the combination of an ERAP1 inhibitor and anti-PD-1 in the CT26 model drove a significant increase in T cell infiltration into the tumor in conjunction with elevated intra-tumoral Granzyme. Finally, the treatment combination led to a significant elevation of a broad range of translationally relevant immune markers that have been shown to correlate with patient response to anti-PD-1 treatment, including CXCL9, CXCL10, IFNg and IL-7R.

It is important to note that this impact on immune markers is tumor-specific as it was only observed within tumors and not in the periphery, suggesting that ERAP1 inhibition is driving an entirely novel, cancer-specific response.

Tumor Growth Inhibition

The ability of ERAP1 inhibition to drive neoantigen creation and the subsequent differentiated T cell response resulted in a meaningful impact on tumor growth. Presented study results demonstrated clear tumor growth inhibition and improved overall survival in multiple syngeneic mouse models following treatment with ERAP1 inhibitors in combination with an anti-PD-1 antibody, as compared to vehicle. Significantly, in the CT26 syngeneic mouse model, each of the findings demonstrating a differentiated T cell response (i.e., TCR repertoire changes, T cell infiltration and upregulation of translationally relevant immune markers) correlates with tumor growth inhibition providing compelling evidence for neoantigen creation driving anti-tumor responses.

"The totality of these presented data provides compelling support for our belief that the generation of novel neoantigens through targeted inhibition of ERAP1 represents a promising, entirely new approach to the oncology drug development space. While we have previously shown the potential of our ERAP1 inhibitors to generate neoantigens that drive anti-tumor responses, these new data presented today clearly demonstrate that the anti-tumor responses are due to a novel and differentiated T cell response," said Peter Joyce, Ph.D., chief executive officer of Grey Wolf Therapeutics. "While these promising results were achieved by combining our ERAP1 inhibitors with an anti-PD-1 antibody, it is important to note that we believe our unique approach will be orthogonal to a broad range of other cancer therapy modalities, including, but not limited to, immunotherapy. Based on these data, we continue to progress our lead ERAP1 inhibitor drug candidate through preclinical development, with the goal of advancing into the clinic in the second half of 2022."

Grey Wolf Therapeutics is developing a portfolio of ERAP inhibitors that it believes represents the first ever application of direct neoantigen generation to the treatment of cancer. GRWD5769, the company’s lead ERAP1 inhibitor development candidate, is expected to enter the clinic in the second half of 2022.

On November 12, 2021, NantHealth, Inc. (the "Company") reported that it entered into an Open Market Sale Agreement (the "Sale Agreement") with Jefferies LLC (the "Sales Agent") under which it may offer and sell up to $30,000,000 of shares of its common stock, par value $0.0001 per share (the "Shares"), from time to time through the Sales Agent (Filing, 8-K, NantHealth, NOV 12, 2021, View Source [SID1234595514]). The sales and issuances of the Shares under the Sale Agreement will be made pursuant to the Company’s effective shelf registration statement on Form S-3 (the "Registration Statement") that was declared effective on May 6, 2021. The offering is described in the Company’s Prospectus, as supplemented by a Prospectus Supplement dated November 12, 2021, as filed with the U.S. Securities and Exchange Commission (the "SEC") on November 12, 2021 (together, the "Prospectus").

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Pursuant to the Sale Agreement, sales, if any, of the Shares, will be made under the Prospectus, by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415(a)(4) under the Securities Act of 1933, as amended (the "Securities Act"), including block transactions, sales made directly on the Nasdaq Global Select Market or sales made into any other existing trading market for the registrant’s common stock. The Sales Agent is not required to sell any specific amount of securities, but will act as our sales agent using commercially reasonable efforts to sell the Shares from time to time, consistent with their normal trading and sales practices, applicable state and federal laws, rules and regulations and the rules of The Nasdaq Global Select Market, based upon instructions from the Company (including any price, time or size limits or other customary parameters or conditions the Company may impose). The Company has agreed to pay the Sales Agent a commission of 3.0% of the aggregate gross proceeds from each sale of Shares pursuant to the Sale Agreement and to provide the Sales Agent with customary indemnification and contribution rights, including for liabilities under the Securities Act. The Sales Agent’s obligations to sell the Shares under the Sale Agreement are subject to satisfaction of certain conditions, including customary closing conditions.

The Company is not obligated to sell any Shares under the Sale Agreement and may at any time suspend solicitation and offers under the Sale Agreement. The Sale Agreement may be terminated by either party as set forth in the Sale Agreement.

The foregoing description of the Sale Agreement is not complete and is qualified in its entirety by reference to the full text of the Sale Agreement, a copy of which is filed herewith as Exhibit 10.1 to this Current Report on Form 8-K and is incorporated herein by reference.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Wilson Sonsini Goodrich & Rosati, Professional Corporation, counsel to the Company, has issued a legal opinion relating to the validity of the Shares being offered pursuant to the Sale Agreement. A copy of such legal opinion, including the consent included therein, is filed as Exhibit 5.1 to this Current Report on Form 8-K and is incorporated herein by reference.

On November 12, 2021 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in cell therapy to treat cancer, reported that it will present translational data from the Phase 1 SURPASS trial during the poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in Washington, D.C. (or virtual) (Abstract #373) from November 12-14, 2021 (Press release, Adaptimmune, NOV 12, 2021, View Source [SID1234595373]). In addition, the Company will present a data update from four patients treated in the radiation sub-study of the Phase 1 trial with afami-cel (Abstract #376).

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"The SURPASS data show that the addition of AKTi along with next-gen enhancements results in an improved and more potent SPEAR T-cell product," said Karen Miller, Adaptimmune’s Senior Vice President, Pipeline Research. "The data we continue to generate in the Phase 1 SURPASS trial shows promising responses for patients across multiple solid tumor indications. We will continue to explore more next-gen enhancements and manufacturing improvements, informed by our ongoing translational research, to deliver the best cell therapies we can for people with cancer."

Addition of AKTi during manufacturing results in improved phenotype and proliferative potential of SPEAR T-cells – attributes that may contribute to more sustained antitumor immune responses

In vitro analyses of manufactured product samples

ADP-A2M4CD8 SPEAR T-cells were manufactured with and without AKTi
Samples manufactured with AKTi expanded more effectively during manufacturing compared to samples without
Flow cytometry analyses of ADP-A2M4CD8 SPEAR T-cells demonstrated increased stem cell memory content of the transduced population in samples manufactured in the presence of AKTi compared to those manufactured without
This increased stem cell memory content may be beneficial in generating a more sustained immune response in patients
Further experiments were conducted to evaluate the impact of AKTi on SPEAR T-cell manufacturing: surplus pre-infusion apheresis material from patients in the Phase 1 trial of afami-cel trial was remanufactured into research-grade afami-cel with or without AKTi
In vitro functional analyses showed that manufacturing afami-cel SPEAR T-cells with AKTi can remodel gene expression in favor of improved proliferation or cytotoxicity
Post-infusion analyses

ADP-A2M4CD8 SPEAR T-cells manufactured with AKTi demonstrated higher median persistence in peripheral blood of patients in the Phase 1 SURPASS trial, by peak vector copy number and by peak percent recovery, compared to those manufactured without
Serum cytokine responses, measured in peripheral blood of patients who received product manufactured with AKTi (n=14) showed similar or greater induction of host immune response compared to those who received product without AKTi (n=6)
Radiation sub-study (closed to enrollment in July 2021) of the Phase 1 trial with afami-cel

As of December 27, 2020 (data cut-off), 4 patients received low-dose radiation and afami-cel
Overall response rate was 33%, 1 partial response (PR) (melanoma; reported in 2019) out of 3 evaluable patients
Disease control rate was 100%, 1 PR, 2 stable diseases (SD) (1 patient with ovarian and 1 patient with head and neck cancer) out of 3 evaluable patients
Serum cytokine profiles were consistent with afami-cel monotherapy, confirming no apparent impact of low-dose radiation on persistence and peripheral immune response.
There was greater detection of SPEAR T-cells in tumor biopsies when infusion followed low-dose radiation, compared to samples from patients who received afami-cel monotherapy in the Phase 1 trial

On November 12, 2021 Cyteir Therapeutics, Inc. ("Cyteir") (Nasdaq: CYT), a company focused on the discovery and development of next-generation synthetically lethal therapies for cancer, reported financial results for the third quarter ended September 30, 2021 and provided an update on recent business highlights (Press release, Cyteir Therapeutics, NOV 12, 2021, View Source [SID1234595389]).

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"We continue to make significant progress in advancing the Phase 1/2 study of our lead program, CYT-0851, as we reached an important milestone with the identification of the Phase 2 dose," said Markus Renschler, MD, President and Chief Executive Officer of Cyteir. "The Cyteir team is excited to continue with the next steps of CYT-0851 clinical development as we advance the drug into the Phase 2 expansion cohorts as a monotherapy and as we initiate Phase 1 combination therapy with standard chemotherapy, with the ultimate goal of bringing the drug to patients in need."

Third Quarter and Recent Developments Business Review and Operational Updates

CYT-0851

Cyteir completed the dose-escalation portion of its Phase 1/2 study of CYT-0851 up to the maximum feasible daily dose of 1200 mg and declared the maximum tolerated dose of 600mg per day. Dose limiting toxicities of fatigue, vomiting, dehydration, dry skin, stomatitis, myalgia, and acidosis were observed at daily doses of 600mg and above. All were grade 3 events and reversible with dose interruption.

With the dose escalation portion of the study complete, the Phase 2 dose has been identified as 400 mg per day. We continue to enroll patients at the 400mg per day dose and below, to obtain additional safety, pharmacokinetic, and biomarker data. Simultaneously, we are initiating Phase 2 expansion study into disease-specific cohorts and expect to begin enrolling patients in the first quarter of 2022. We are also initiating a Phase 1 combination study of CYT-0851 with three standard-of-care regimens: rituximab plus bendamustine, gemcitabine and capecitabine, in both hematologic malignancies and solid tumors.

Pipeline

Investigational New Drug (IND)-enabling studies with CYT-1853 are ongoing and the Company expects to submit an IND application for CYT-1853 in 2022. Cyteir is also advancing preclinical studies on additional targets to nominate the next target from the Company’s DNA damage response platform.

Third Quarter Financial Results

Cash and cash equivalents: Cash and cash equivalents for the quarter ended September 30, 2021, were $199.8 million. The cash and cash equivalents total for the third quarter includes the $14.5 million in net proceeds raised from the partial exercise of the option to purchase additional shares of common stock by the underwriters of our IPO.

Research and development (R&D) expenses: R&D expenses were $8.2 million for the third quarter of 2021 versus $4.2 million for the same period in 2020. The year-over-year increase in R&D spending in the comparative periods was due primarily to increased R&D and clinical activity and increased headcount.

General and administrative (G&A) expenses: G&A expenses were $3.5 million for the third quarter of 2021 compared to $0.8 million for the same period in 2020. The year-over-year increase in G&A expenses in the comparative periods was primarily due to increased headcount, as well as increased professional fees and other administrative expenses associated with company growth and operating as a public company.

Net loss: Net loss was $11.7 million, or $0.33 per share in the third quarter of 2021 compared to $5.0 million, or $3.44 per share in the third quarter of 2020.