On January 21, 2020 Cue Biopharma, Inc. (NASDAQ: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells within the body, reported the publication of research demonstrating the ability of its lead biologic candidate CUE-101 to activate tumor antigen specific antitumor immunity in the peer-reviewed medical journal Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Cue Biopharma, JAN 21, 2020, View Source [SID1234608306]). The manuscript by Steven Quayle et al. is titled "CUE-101, a Novel HPV16 E7 pHLA-IL-2-Fc Fusion Protein, Enhances Tumor Antigen Specific T Cell Activation for the Treatment of HPV16-Driven Malignancies." (http://bit.ly/2twfkxd)

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The research highlights the ability of the company’s proprietary Immuno-STAT (Selective Targeting and Alternation of T cells) platform to selectively engage and modulate targeted T cells within the body. CUE-101 is the company’s lead drug candidate from the IL-2 based CUE-100 series designed to directly engage and activate T cells to target HPV16-driven recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

The published results show that CUE-101 demonstrated selective binding, activation and expansion of the disease-relevant human T cell population in vitro, as well as predict a favorable safety profile. A murine surrogate molecule (mCUE-101) administered to HPV16 E7 tumor bearing mice resulted in selective expansion of disease-relevant T cells, anti-cancer efficacy and immunologic memory. In addition, mCUE-101 administered as a combination therapy with anti-PD-1 checkpoint inhibition further enhanced anti-tumor efficacy. These data support the potential for CUE-101 to enhance anti-tumor immunity in HPV16-driven malignancies. CUE-101 is currently being studied in a Phase 1 clinical trial (NCT03978689) for HPV16-driven HNSCC. The Phase 1 trial is evaluating the safety and tolerability, anti-tumor response, pharmacokinetics and immunogenicity of CUE-101 as a monotherapy in patients with confirmed HPV16-driven recurrent/metastatic HNSCC and HLA-A*02:01 serotype. Based on results from this trial, including translational pharmacodynamic immunoprofiling data, the company may expand the study to test CUE-101 in the neoadjuvant setting and in combination with checkpoint inhibitors in patients with HPV16-driven HNSCC.

"This seminal publication from Cue Biopharma exemplifies the core-strength of our Immuno-STAT biologics platform, in particular the CUE-100 series that incorporates rationally engineered IL-2 molecules for selective activation of tumor-specific T cells. The preclinical and ex vivo human translational data presented in this paper underscore the promising potential for the current, ongoing clinical study evaluating CUE-101 monotherapy in HPV-driven head and neck cancer," stated Anish Suri, Ph.D., president and chief scientific officer of Cue Biopharma.

HPV-driven cancers account for more than 20,000 deaths each year in the U.S. and Europe. The majority of these cancers are driven by HPV16 which carries the E7 protein targeted by CUE-101. Despite treatment with current standards of care, approximately 50% of patients with advanced disease will experience recurrence and significant quality of life impact. Patients with HPV-driven cancers represent an important unmet clinical need and underscore the opportunity for promising new therapeutics.

Clinical Cancer Researchis a peer-reviewed medical journal published by the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The journal publishes innovative clinical and translational cancer research studies that bridge the laboratory and the clinic.

About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This singular biologic is anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.

About Immuno-STAT
Immuno-STAT biologics are designed for targeted modulation of disease-associated T cells in the areas of immuno-oncology and autoimmune disease. Each of our biologic drugs is designed using our proprietary scaffold comprising: 1) a peptide-MHC complex (pMHC) to provide selectivity through interaction with the T cell receptor (TCR), and 2) a unique co-stimulatory signaling molecule to modulate the activity of the target T cells.

The simultaneous engagement of co-stimulatory molecules and pMHC binding mimics the signals delivered by antigen presenting cells (APCs) to T cells during a natural immune response. This design enables Immuno-STAT biologics to engage with the T cell population of interest, resulting in highly targeted T cell modulation. Because our drugs are delivered directly in the patient’s body (in vivo), they are fundamentally different from other T cell therapeutic approaches that require the patients’ T cells to be extracted, stimulated and expanded outside the body (ex vivo), and reinfused in an activated state.

On January 21, 2020 Rafael Pharmaceuticals, Inc. ("Rafael" or the "Company"), a leader in the growing field of cancer metabolism-based therapeutics, reported its collaboration with Michigan Medicine to proceed with a Phase 1b/2 clinical trial of CPI-613 (devimistat) in combination with gemcitabine and cisplatin for patients with biliary tract cancer (Press release, Rafael Pharmaceuticals, JAN 21, 2020, View Source [SID1234553562]). The study will be a multicenter randomized trial of gemcitabine and cisplatin with or without devimistat as a first-line therapy for patients with locally advanced, unresectable or metastatic biliary tract cancer who have had no prior treatment.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The goal of the Phase 1b part of the trial will be to identify the maximum tolerated dose (MTD), or the highest dose of devimistat that does not cause side effects, when given in combination with gemcitabine and cisplatin. This will determine the recommended dose for the randomized Phase 2 part of the trial. The goal of Phase 2 will be to then determine the efficacy of devimistat in combination with gemcitabine and cisplatin as compared with the combination chemotherapy alone. An estimated 68 to 78 patients will be enrolled in the study.

"Biliary tract cancer is a rare and aggressive cancer that affects approximately 15,000 people in the United States each year," said Sanjeev Luther, President and CEO of Rafael Pharmaceuticals. "Launching this trial aligns with our mission to help patients with significant unmet medical needs."

Vaibhav Sahai, MBBS, MS., Associate Professor of Medical Oncology at Michigan Medicine, is the Principal Investigator on the study.

"Devimistat has demonstrated promising results in pancreatic cancer," said Dr. Sahai. "Rare cancers require dedicated and innovative research, and I am hopeful that we will advance treatment options for patients with biliary tract cancer."

About CPI-613 (devimistat)

CPI-613 (devimistat) is a first-in-class clinical lead compound of Rafael, which targets enzymes that are involved in cancer cell energy metabolism and are located in the mitochondria of cancer cells. Devimistat is designed to target the mitochondrial tricarboxylic acid (TCA) cycle, a process essential to tumor cell multiplication and survival, selectively in cancer cells. Devimistat substantially increases the sensitivity of cancer cells to a diverse range of chemotherapeutic agents. This synergy allows for potential combinations of devimistat with lower doses of these generally toxic drugs to be more effective with lower patient’s side effects. Combination with devimistat represent a diverse range of opportunities to substantially improve patient’s benefit in many different cancers. The U.S. Food and Drug Administration (FDA) has given Rafael approval to initiate pivotal Phase 3 clinical trials in pancreatic cancer (AVENGER 500) and acute myeloid leukemia (ARMADA 2000), and has designated devimistat as an orphan drug for the treatment of pancreatic cancer, acute myeloid leukemia, myelodysplastic syndrome, peripheral T-cell lymphoma and Burkitt’s lymphoma. The EMA has granted orphan drug designation to devimistat for pancreatic cancer and acute myeloid leukemia.

On January 21, 2020 REVOLUTION Medicines, Inc., a clinical-stage leader in the discovery and development of novel small molecule inhibitors of frontier oncology targets within notorious pathways, reported that it had filed to raise $100 million in IPO on Nasdaq. (Press release, Revolution Medicines, JAN 21, 2020, View Source [SID1234553553])

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Company Description

We are a clinical-stage precision oncology company focused on developing novel targeted therapies to inhibit elusive, high-value frontier targets within notorious growth and survival pathways, with particular emphasis on the RAS and mTOR signaling pathways. We define frontier targets as proteins that play an important role in cancer and for which there is either: no approved drug that directly inhibits it, or one or more approved drugs that directly inhibit it but through a mechanism of action that may not enable suppression of the full range of its biologic contributions to cancer. Our understanding of genetic drivers and adaptive resistance mechanisms in cancer, coupled with robust drug discovery and medicinal chemistry capabilities, has guided us to establish a deep pipeline targeting critical signaling nodes within these pathways. This cohesive approach underpins our clinical strategy of exploring mechanism-based dosing paradigms and in-pathway combinations to optimize treatment for cancer patients.

Our most advanced product candidate, RMC-4630, is a potent and selective inhibitor of SHP2, based on preclinical evidence described in this prospectus. SHP2 is a central node in the RAS signaling pathway. In collaboration with Sanofi, we are evaluating RMC-4630 in a multi-cohort Phase 1/2 clinical program. This RMC-4630 Phase 1/2 program currently consists of two active clinical trials: RMC-4630-01, a Phase 1 study of RMC-4630 as a single agent, and RMC-4630-02, a Phase 1b/2 study of RMC-4630 in combination with the MEK inhibitor cobimetinib (Cotellic). In this prospectus, we report preliminary data from 63 patients who had enrolled in our Phase 1 study and received RMC-4630 as monotherapy as of November 6, 2019 and from eight patients who had enrolled in our Phase 1b/2 combination study and received RMC-4630 as of November 14, 2019. Leveraging our proprietary tri-complex technology platform, we are also developing a portfolio of mutant-selective RAS inhibitors that we believe are the first potent, selective, cell-active inhibitors of the active, GTP-bound form of RAS, or RAS(ON). These inhibitors also have exhibited anti-tumor activity in vivo in preclinical models.

Initially, we will prioritize four mutant RAS(ON) targets—KRASG12C, KRASG13C, KRASG12D and NRASG12C—and expect to nominate our first development candidate in 2020. Our pipeline also includes inhibitors of other key nodes within the RAS and mTOR signaling pathways, such as SOS1 and mTORC1. Our pipeline includes one product candidate that is in clinical development and all of our other programs are in the preclinical stage. We believe our deep, differentiated pipeline and development strategies provide us with the opportunity to pioneer novel treatment regimens to maximize the depth and durability of clinical benefit and circumvent adaptive resistance mechanisms for patients with cancers dependent on these critical pathways.

— Under our collaboration on our SHP2 program with Sanofi, we have a 50-50 profit share and a co-promote right in the United States and are eligible to receive royalties on net sales outside of the United States. Sanofi is responsible for reimbursing substantially all of our research costs and all of our development costs for the SHP2 program. For all other programs, we retain worldwide commercial rights. —

On January 21, 2020 Adaptive Biotechnologies Corporation (Nasdaq:ADPT), a commercial stage biotechnology company that aims to translate the genetics of the adaptive immune system into clinical products to diagnose and treat disease, reported the commencement of a proposed underwritten public offering of 8,000,000 shares of its common stock by certain selling shareholders (Press release, Adaptive Biotechnologies, JAN 21, 2020, View Source [SID1234553523]). In addition, certain selling shareholders expect to grant the underwriters a 30-day option to purchase up to an additional 1,200,000 shares of its common stock in the offering. Adaptive will not receive any of the proceeds from the sale of the shares of its common stock being offered by the selling shareholders. The proposed offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

J.P. Morgan, Goldman Sachs & Co. LLC and BofA Securities are acting as joint lead book-running managers for the offering. Cowen, Guggenheim Securities and William Blair are acting as book-running managers for the offering. BTIG is acting as co-manager for the offering.

A registration statement on Form S-1 relating to these securities has been filed with the U.S. Securities and Exchange Commission (SEC) but has not yet become effective. These securities may not be sold nor may offers to buy these securities be accepted prior to the time the registration statement becomes effective. The offering will be made only by means of a prospectus. A copy of the preliminary prospectus relating to this offering may be obtained from: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204 or by email at [email protected]; Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at (866) 471-2526, or by email at [email protected]; or BofA Securities, Inc., NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, NC 28255-0001, Attn: Prospectus Department, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these 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.

On January 21, 2020, Vaccinex, Inc. (the "Company"), reported that it has entered into a stock purchase agreement (the "Stock Purchase Agreement") with certain investors as indicated on Exhibit A to the Stock Purchase Agreement (the "Investors"), pursuant to which the Company agreed to issue and sell to the Investors, and the Investors agreed to purchase from the Company, an aggregate of 1,468,563 shares (the "Shares") of common stock, par value $0.0001 per share, of the Company (the "Common Stock"), at a purchase price of $5.09 per Share (the average closing price for the common stock for the five trading days immediately preceding the date of the Stock Purchase Agreement) (the "Private Placement") (Filing, 8-K, Vaccinex, JAN 21, 2020, View Source [SID1234553464]). The Stock Purchase Agreement contains customary representations and warranties of the parties. The closing of the Private Placement occurred on January 23, 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The aggregate gross proceeds for the sale of the Shares was $7,474,985.67. The Company intends to use the net proceeds from the Private Placement to fund the ongoing development of pepinemab, the Company’s lead product candidate, and for working capital and general corporate purposes.

FCMI Parent Co., one of the Investors, is the Company’s majority stockholder and is controlled by Albert D. Friedberg, the Company’s chairman. Vaccinex (Rochester), L.L.C., of which Dr. Maurice Zauderer, the Company’s president, chief executive officer and a member of its board of directors, is the president and a majority owner, is another Investor. Jacob Frieberg, a third Investor, is one of the Company’s current directors.

The Shares have not been registered under the Securities Act of 1933, as amended (the "1933 Act"), and were issued and sold in a private placement pursuant to Section 4(a)(2) of the 1933 Act and Rule 506 of Regulation D as promulgated by the Securities and Exchange Commission (the "SEC") under the 1933 Act. Each of the Investors represented that it is an "accredited investor" within the meaning of Rule 501 of Regulation D, and is acquiring the Shares for investment only and not with a view towards, or for resale in connection with, the public sale or distribution thereof. The Shares were offered without any general solicitation by the Company or its representatives.

On January 23, 2020, the Company entered into a registration rights agreement (the "Registration Rights Agreement") with the Investors that affords the Investors certain registration rights with respect to the Shares. Under the Registration Rights Agreement, the Company has agreed, among other things, to use its reasonable best efforts to file with the SEC a registration statement covering the resale of the Shares by the later of 60 days from the closing of the Private Placement and March 31, 2020 and commercially reasonable efforts to cause such registration statement to become effective on or prior to 90 calendar days (or, in the event of a substantive review by the SEC, 135 calendar days) from the closing date. In addition, the Company agreed to use commercially reasonable efforts to keep the registration statement effective until the Shares have been sold thereunder or until the Shares can be sold without restriction. If the Company fails to meet the specified deadlines for the effectiveness of the registration statement, the Company will be required to pay liquidated damages to the Investors, subject to maximum aggregate liquidated damages of 8.0% of the aggregate purchase price paid for the Shares. Interest on any unpaid

liquidated damages will accrue at a rate of 1.0% per month. In addition, the Company agreed to provide Investors with certain "piggy-back" registration rights that may require the Company to effect certain registrations to register the Shares for resale in the event that no registration statement registering the Shares is effective and the Company is otherwise filing a registration statement under the 1933 Act.

The Registration Rights Agreement also contains certain indemnification and contribution provisions under which the Company and the Investors have agreed to indemnify each other against certain liabilities.

The foregoing summaries of the Stock Purchase Agreement and the Registration Rights Agreement do not purport to be complete and are subject to and qualified in their entirety by the terms of the Stock Purchase Agreement and the Registration Rights Agreement, copies of which are attached hereto as Exhibit 10.1 and Exhibit 10.2, respectively, and are incorporated by reference herein.