On January 26, 2024, Aprea Therapeutics, Inc. (the "Company") reported to have entered into an at the market offering agreement (the "Sales Agreement") with H.C. Wainwright & Co., LLC (the "HCW") (Press release, Aprea, JAN 26, 2024, View Source [SID1234639543]). Under the Sales Agreement, the Company may offer and sell its common stock, par value $0.001 per share ("Common Stock"), from time to time having an aggregate offering price of up to $1.0 million (the "Shares") during the term of the Sales Agreement through or to HCW as sales agent or principal. The Company has filed a prospectus supplement relating to the offer and sale of the Shares pursuant to the Sales Agreement. The offering and sale of the Shares will be made pursuant to the Company’s Registration Statement on Form S-3, filed with the Securities and Exchange Commission (the "SEC") on January 26, 2024. The Shares may be offered only by means of a prospectus forming a part of the Registration Statement. The Company intends to use the net proceeds from the offering, if any, for general corporate purposes, including for preclinical studies and clinical trials and the advancement of our product candidates.

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The Company is not obligated to sell any Shares pursuant to the Sales Agreement. Subject to the terms and conditions of the Sales Agreement, HCW will use commercially reasonable efforts, consistent with its normal trading and sales practices and applicable state and federal law, rules and regulations, to sell Shares from time to time based upon the Company’s instructions, including any price, time or size limits or other customary parameters or conditions the Company may impose.

Under the Sales Agreement, HCW may sell Shares by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415 of the Securities Act of 1933, as amended, and the rules and regulations thereunder.

The Sales Agreement may be terminated by either party providing notice, subject to the limitations set forth in the Sales Agreement.

The Company has agreed to pay HCW a commission equal to 3.0% of the gross proceeds from the sales of Shares pursuant to the Sales Agreement and has agreed to provide HCW with customary indemnification and contribution rights.

The foregoing summary of the Sales Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which is filed as Exhibit 1.1 hereto and incorporated herein by reference. The Sales Agreement contains representations and warranties that the parties made to, and solely for the benefit of, the other in the context of all of the terms and conditions of the Sales Agreement and in the context of the specific relationship between the parties. The provisions of the Sales Agreement, including the representations and warranties contained therein, are not for the benefit of any party other than the parties to the Sales Agreement and are not intended as a document for investors and the public to obtain factual information about the Company’s current state of affairs. Rather, investors and the public should look to other disclosures contained in the Company’s filings with the SEC.

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

On January 25, 2024, HOOKIPA Pharma Inc. ("HOOKIPA") received written notice (the "Notice") from F. Hoffmann-La Roche Ltd. and Hoffmann-La Roche Inc. (collectively referred to as "Roche") of their decision to terminate the Research Collaboration and License Agreement (the "Collaboration Agreement") among Roche and Hookipa Biotech GmbH ("HOOKIPA GmbH," and together with HOOKIPA, the "Company"), a wholly-owned subsidiary of HOOKIPA, dated October 18, 2022 (Filing, Hoffmann-La Roche, JAN 25, 2024, View Source [SID1234642009]). Roche’s decision to terminate the Collaboration Agreement was made according to Roche’s right to terminate without cause, acknowledging that, to date, HOOKIPA met all go-forward criteria under the Collaboration Agreement.

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The Collaboration Agreement was entered into to (i) grant Roche an exclusive license to research, develop, manufacture and commercialize the Company’s pre-clinical HB-700 cancer program, an arenaviral immunotherapeutic for KRAS-mutated cancers, and (ii) grant Roche an option right to exclusively license for research, development manufacturing and commercialization, a second, novel arenaviral immunotherapeutic program targeting undisclosed cancer antigens.

Pursuant to the terms of the Collaboration Agreement and the Notice, the Collaboration Agreement will be terminated on April 25, 2024. The Company remains eligible for a final milestone payment associated with an IND submission. Effective April 25, 2024, the Company will regain full control of the associated intellectual property portfolio and will have full collaboration and licensing rights for the HB-700 program. After the termination of the Collaboration Agreement, and except as disclosed above, there is no other material relationship between the Company and Roche.

On January 25, 2024 Be Biopharma, Inc. ("Be Bio"), a company pioneering the development of engineered B Cell Medicines (BCMs), reported an oral presentation and poster presentation at the Keystone Symposia on Emerging Cellular Therapies meeting, held from January 22 to 25, 2024 in Santa Fe, New Mexico (Press release, Be Biopharma, JAN 25, 2024, View Source [SID1234639549]). The data being presented support the utility of engineered B cell medicines (BCMs) across a broad range of applications. Together, the data demonstrate in vitro production and activity of several therapeutic proteins, as well as in vivo engraftment without preconditioning and activity in multiple model systems.

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"Gene and cell therapies have transformative potential to treat previously intractable diseases, but have barriers to adoption such as lack of durability, inability to re-dose, and requirement of preconditioning for engraftment. Our BCM platform has the potential to address these barriers," said Richard A. Morgan, Ph.D., Chief Scientific Officer, Be Bio. "The in vivo preclinical data presented today validates key attributes of our BCM platform – efficient protein production, editing and insertional efficiency, and durable protein production without preconditioning – while demonstrating its potential therapeutic benefits in genetic disease and cancer."

Presentation Summary: Development of an Ex Vivo Precision Gene Engineered B Cell Medicine Platform that Produces Active and Sustained Levels of Therapeutic Proteins with Broad Utility

BCMs were produced via a precision genome engineering platform that achieves gene knockouts with greater than 90% efficiency and targeted HDR-mediated gene insertions at up to 60%. Modularity of the BCM platform was demonstrated across multiple models and proteins, including production of firefly luciferase, lysosomal storage disease enzyme acid sphingomyelinase, an anti-CD19/CD3 bispecific T cell engager, clotting factor IX, and fusion protein of tissue nonspecific alkaline phosphatase (ALP). These examples demonstrate that these BCMs can produce proteins with enzyme specific activity higher than recombinant proteins (ASM), show efficacy in tumor treatment (anti-CD19/CD3 scFv), and are stably expressed for at least 20 weeks in vivo (FIX). Engraftment in all models was achieved without preconditioning which broadens BCM clinical utility for patients for whom preconditioning toxicities are unacceptable or outweigh therapeutic benefit, and could facilitate additional rounds of treatment as needed. BCMs capable of expressing therapeutically relevant transgenes have the potential for broad and meaningful therapeutic utility in genetic diseases, cancer, and beyond.

Details for the oral presentation of this study are as follows:

Title: "Development of an Ex Vivo Precision Gene Engineered
B Cell Medicine Platform that Produces Active and Sustained Levels of Therapeutic Proteins with Broad Utility"

Lead Author: Hanlan Liu, Ph.D., MBA, Senior VP, Pipeline and Non-clinical Development, Be Biopharma

Presenter: Hanlan Liu, Ph.D., MBA, Senior VP, Pipeline and Non-clinical Development, Be Biopharma

Date/Time: Tuesday, January 23, 2024, 5:00-7:00pm (MST)

Session: Strategies for Engineered Cell Therapies

Poster Summary: Development of an Ex Vivo Precision Gene Engineered B Cell Medicine Platform that Produces Active and Sustained Levels of Therapeutic Proteins with Broad Utility in Rare Diseases and Cancer

This study demonstrates production of BCMs via editing, expansion and differentiation of primary human B cells. Cells engineered to express firefly luciferase were engrafted into NOG-hIL6 mice and demonstrated in vivo persistence for 125 days. Data are also presented on BCMs engineered to produce FIX, which demonstrates activity via the chromogenic and aPTT assay. These BCMs were engrafted into NOG-hIL6 mice and demonstrate durable FIX secretion to 168 days. In addition to FIX, BCMs were engineered to produce an anti-CD19/CD3 bispecific T cell engager, which demonstrated potent activity in an in vivo PdX model of ALL, ALP, which corrected HPP-related bone mineralization deficits in vitro, and ASM, which demonstrated in vitro phenotypic correction in SMPD1 knockout cells. In addition, ex vivo-rhesus macaque plasma cells were generated and labeled with a radioactive tracer. These cells were administered without preconditioning and demonstrated homing to and engraftment in plasma cell niches in an autologous rhesus macaque.

Details for the poster presentation of this study are as follows:

Title: "Development of an Ex Vivo Precision Gene Engineered B Cell Medicine Platform that Produces Active and Sustained Levels of Therapeutic Proteins with Broad Utility in Rare Diseases and Cancer"

Lead Author: Hanlan Liu, Ph.D., MBA, Senior VP, Pipeline and Non-clinical Development, Be Biopharma

Presenter: Hanlan Liu, Ph.D., MBA, Senior VP, Pipeline and Non-clinical Development, Be Biopharma

Poster #: 2

Poster Session: Wednesday, January 24, 2024, 7:30pm (MST)

About Engineered B Cell Medicines – A New Class of Cellular Medicines

The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas.

On January 25, 2024 ArriVent BioPharma, Inc. ("ArriVent") (Nasdaq: AVBP), a clinical-stage company dedicated to accelerating the global development of innovative biopharmaceutical therapeutics, reported the pricing of its upsized initial public offering of 9,722,222 shares of its common stock at a public offering price of $18.00 per share (Press release, ArriVent Biopharma, JAN 25, 2024, https://arrivent.com/arrivent-announces-pricing-of-upsized-initial-public-offering/?utm_source=rss&utm_medium=rss&utm_campaign=arrivent-announces-pricing-of-upsized-initial-public-offering [SID1234639545]). All of the shares of common stock are being offered by ArriVent. The gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by ArriVent, are expected to be approximately $175.0 million. ArriVent’s common stock are expected to begin trading on the Nasdaq Global Market on January 26, 2024 under the ticker symbol "AVBP." The offering is expected to close on January 30, 2024, subject to the satisfaction of customary closing conditions. In addition, ArriVent has granted the underwriters a 30-day option to purchase up to an additional 1,458,333 shares of its common stock at the initial public offering price, less underwriting discounts and commissions.

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Goldman Sachs & Co. LLC, Jefferies and Citigroup are acting as joint book-running managers for the offering. LifeSci Capital is acting as the lead manager for the offering.

Registration statements relating to the shares being sold in this offering have been filed with the Securities and Exchange Commission (the "SEC") and became effective on January 25, 2024. Copies of the registration statements can be accessed through the SEC’s website at www.sec.gov. This offering is being made only by means of a written prospectus. A copy of the final prospectus related to the offering will be filed with the SEC, and may be obtained, when available, from: Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, via telephone: (866) 471-2526, or via email: [email protected]; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, via telephone: (877) 821-7388, or via email: [email protected]; or Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 or via telephone: (800) 831-9146.

This press release does not constitute an offer to sell or the solicitation of an offer to buy these securities, nor will there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state, province, territory or other jurisdiction.

On January 25, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported the publication of two new studies in Nature Medicine evaluating Natera’s personalized and tumor-informed molecular residual disease (MRD) test, Signatera (Press release, Natera, JAN 25, 2024, View Source [SID1234639490]).

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The first study shows results from the single-arm, phase I AMPLIFY-201 trial evaluating the ELI-002 cancer vaccine. The study enrolled a total of 25 patients (20 pancreatic, 5 colorectal), 21 of whom were Signatera-positive after locoregional treatment. Signatera dynamics were also used as a secondary endpoint to assess tumor biomarker response, together with serum tumor antigens. This study is the first of its kind to have utilized circulating tumor DNA (ctDNA)-positivity in conjunction with other tumor biomarkers for enrollment, highlighting the use of Signatera for detecting early evidence of anti-tumor activity of a drug candidate to help assess for a dose response.

The study reported that tumor biomarker responses were observed in 21/25 patients (84%), and ctDNA clearance was observed in 6/25 patients (24%). In contrast, serum tumor antigens declined but did not clear, highlighting the potential utility of ctDNA to be used as a reliable surrogate biomarker for treatment efficacy.

"We are excited about our partnership with Natera, which has resulted in a successful prospective, phase I clinical trial focused on trial enrichment by enrolling Signatera-positive patients and monitoring therapy response in patients receiving a cancer vaccine," said Christopher Haqq, MD, PhD, Elicio Therapeutic, Inc’s executive vice president, head of research and development, and chief medical officer. "We are optimistic about the potential for this study to improve outcomes for patients with pancreatic and colorectal cancer, who face clinical challenges and are often incurable when ctDNA is detected after treatment."

A second study published in Nature Medicine, called PANDA, is a single-arm, open-label, phase II study that investigated preoperative atezolizumab plus chemotherapy in patients with resectable, non-metastatic gastric and gastroesophageal junction adenocarcinoma. The study included 20 patients who underwent surgery and were evaluated for safety, pathologic response, and survival endpoints, and Signatera was used to detect and monitor ctDNA dynamics in all 20 patients.

The PANDA study found that ctDNA clearance after neoadjuvant therapy correlated with pathologic response in 11/11 patients, while 3/6 patients with poor pathologic response remained ctDNA-positive (P=0.029). None of the patients with complete pathologic response (pCR) were ctDNA-positive, and among the nonresponders who were ctDNA negative (n=3), the study reported superior long-term outcomes. Additionally, ctDNA-positivity at the MRD and follow-up time points was associated with a recurrence rate of 100%.

"We’re pleased to see these excellent results from the PANDA study which demonstrate the strong correlation between ctDNA and pathologic response pre-surgery and the therewith associated recurrence risk, highlighting the potential utility of Signatera in gastric and gastroesophageal cancers," said Myriam Chalabi MD, PhD, medical oncologist, Netherlands Cancer Institute, and principal investigator of the PANDA study.

"PANDA and AMPLIFY-201 add to the growing number of studies supporting the use of Signatera across various GI indications, showing the promise of tumor-informed ctDNA testing to help personalize treatment strategies," said Alexey Aleshin, general manager of oncology and early cancer detection at Natera. "These studies also point to the valuable insights longitudinal ctDNA monitoring can provide in the evaluation of novel therapies."

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard-of-care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer (stage IIb and higher) and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.