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.

On January 25, 2024 Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative positron emission tomography (PET) radiopharmaceuticals, reported results from a sub-analysis of data from the Phase 3 SPOTLIGHT trial (NCT04186845) which investigated the use of POSLUMA (flotufolastat F 18) PET in suspected biochemical recurrence of prostate cancer (Press release, Blue Earth Diagnostics, JAN 25, 2024, View Source [SID1234639489]). The sub-analysis assessed the impact of POSLUMA on treatment plans for patients with recurrent prostate cancer after curative-intent primary therapy. POSLUMA (flotufolastat F 18) injection (formerly referred to as 18F-rhPSMA-7.3) is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.

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Results highlights:

Flotufolastat F 18 PET imaging was positive for recurrent prostate cancer in 84% (81/97) of patients in the sub-analysis.
In 89% (86/97) of patients, management plans were changed following review of the flotufolastat F 18 PET scan results.
91% (78/86) of changes were considered major, defined as a change in the treatment modality.
75% (6/8) of patients whose plans were changed in favor of watchful waiting had a negative flotufolastat F 18 scan.
All patients with management plans that were revised from salvage therapy to non-curative systemic therapy had distant/extrapelvic flotufolastat F 18-avid lesions.
"Recurrent prostate cancer presents challenges, and the ability to determine the extent and location of recurrent disease to inform appropriate clinical management is key for physicians and their patients, as up to 40% of patients who undergo radical prostatectomy, and up to 50% of patients who undergo radiation therapy will develop local or distant recurrences within 10 years," said Przemyslaw Twardowski, MD, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, Calif., on behalf of the SPOTLIGHT Study Group. "The SPOTLIGHT study investigated the diagnostic performance of POSLUMA PET imaging as a potential decision-making aid in assessing suspected biochemical recurrence of the disease. This sub-analysis further examined the impact of POSLUMA PET imaging on patients’ management plans. Results showed that POSLUMA identified recurrence sites in the majority of patients, frequently resulting in major changes to previously planned management plans. Patient treatment based on visualization of POSLUMA-avid lesions has the potential to facilitate optimal targeting of recurrence sites and help patients avoid futile salvage therapy."

"We are very pleased to present these results to the oncology community at ASCO (Free ASCO Whitepaper) GU," said David E. Gauden, D.Phil., Chief Executive Officer of Blue Earth Diagnostics. "POSLUMA represents a new class of high-affinity PSMA-targeted radiopharmaceuticals based on novel radiohybrid technology, and provides physicians with clinically useful information based on its performance at low PSA levels, PSMA binding and low urinary bladder activity. Our product has been added to nationally recognized clinical oncology guidelines for prostate cancer, alongside and for all the same categories as the other currently FDA-approved PSMA PET radiopharmaceuticals. POSLUMA is labeled with the radioisotope fluorine-18 (18F) to leverage high image quality and to enable broad, readily available geographic access for patients via the manufacturing and distribution network of our commercial U.S. manufacturer and distributor, PETNET Solutions Inc, A Siemens Healthineers Company."

The findings were discussed in a moderated poster presentation at the ASCO (Free ASCO Whitepaper) GU 2024 Genitourinary Cancers Symposium (ASCO GU) on January 25, 2024. "Impact of 18F-flotufolastat PET on management of patients with recurrent prostate cancer: Data from the SPOTLIGHT study," was presented by Przemyslaw Twardowski, MD, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, Calif., on behalf of the SPOTLIGHT Study Group. Full session details are available in the ASCO (Free ASCO Whitepaper) GU online program here.

About the study

The sub-analysis of SPOTLIGHT data from the 389 patient study assessed the impact of flotufolastat F 18 on planned treatment after curative-intent primary therapy. The present analysis focused on patients who had a flotufolastat F 18 scan and sufficient data for management plan evaluation. Onsite investigators recorded patients’ management plans before and after flotufolastat F 18 PET. Plans were then categorized as "no change," "major change,"" other change," "additional information required" or "intended plan not valid." A "major change" was defined as a change in treatment modality (e.g., salvage radiation to systemic therapy), while "other change" represented a change within a modality (e.g., modified radiation therapy field). All imaging data were then submitted for blinded image evaluation by 3 central readers.

In total, 97 patients (median [range] PSA: 0.08 [0.09-134.6]] ng/mL) had an evaluable flotufolastat F 18 PET scan and sufficient data to evaluate management plan changes. Most patients, 86/97 (89%) had a change to their management plan post-scan. A "major change" was noted for 78 (80%) patients, while 8 (8.2%) had an "other change." Onsite imaging reads showed that both positive and negative flotufolastat F 18 scans influenced management planning. While 88% of revisions occurred after a positive scan, 75% of those whose management plans were revised to watchful waiting had negative scans. All patients with management plans revised from salvage therapy to non-curative systemic therapy had distant/extrapelvic flotufolastat F 18-avid lesions.
No serious adverse reactions were attributed to flotufolastat F 18 in the SPOTLIGHT study. Overall, 16/389 (4.1%) patients had at least one treatment-emergent adverse event that was considered possibly related/related to flotufolastat F 18. The most frequently reported events were: hypertension: 1.8% (n=7); diarrhea: 1.0% (n=4); injection site reaction: 0.5% (n=2), and headache: 0.5% (n=2).
About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)

Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA) compounds consist of a radiohybrid ("rh") Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells, and they may be radiolabeled with imaging isotopes for PET imaging, or with therapeutic isotopes for therapeutic use – providing the potential for creating a true theranostic technology. Radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Diagnostics received U.S. Food and Drug Administration approval for its radiohybrid PET diagnostic imaging product for use in prostate cancer in 2023. rhPSMA compounds for potential therapeutic use are investigational and have not received regulatory approval.

Indication and Important Safety Information About POSLUMA

INDICATION

POSLUMA (flotufolastat F 18) injection is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer

with suspected metastasis who are candidates for initial definitive therapy
with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level
IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with POSLUMA PET. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of POSLUMA for imaging metastatic pelvic lymph nodes in patients prior to initial definitive therapy seems to be affected by serum PSA levels and risk grouping. The performance of POSLUMA for imaging patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. Flotufolastat F 18 uptake is not specific for prostate cancer and may occur in other types of cancer, in non-malignant processes, and in normal tissues. Clinical correlation, which may include histopathological evaluation, is recommended.
Risk of Image Misinterpretation in Patients with Suspected Prostate Cancer Recurrence: The interpretation of POSLUMA PET may differ depending on imaging readers, particularly in the prostate/prostate bed region. Because of the associated risk of false positive interpretation, consider multidisciplinary consultation and histopathological confirmation when clinical decision-making hinges on flotufolastat F 18 uptake only in the prostate/prostate bed region or only on uptake interpreted as borderline.
POSLUMA use contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Advise patients to hydrate before and after administration and to void frequently after administration. Ensure safe handling to minimize radiation exposure to the patient and health care providers.
The adverse reactions reported in ≥0.4% of patients in clinical studies were diarrhea, blood pressure increase and injection site pain.
Drug Interactions: androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F 18 in prostate cancer. The effect of these therapies on performance of POSLUMA PET has not been established.
To report suspected adverse reactions to POSLUMA, call 1-844-POSLUMA (1-844-767-5862) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full POSLUMA prescribing information is available at www.posluma.com/prescribing-information.pdf.