IN8bio Announces FDA Clearance to Initiate a Phase 2 Clinical Trial of INB-400 Gamma-Delta T Cells for Glioblastoma

On December 8, 2022 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies, reported that it has received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 clinical trial of a genetically modified autologous gamma-delta T cell therapy (INB-400) targeting newly diagnosed glioblastoma (GBM) (Press release, In8bio, DEC 8, 2022, View Source [SID1234624954]). The study will assess the safety, efficacy and tolerability of genetically modified DeltEx drug-resistant immunotherapy (DRI) cells at leading medical centers across the United States.

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"Obtaining clearance to begin the INB-400 Phase 2 clinical trial is an important milestone for IN8bio as it is our first company-sponsored IND. This milestone demonstrates the clinical, regulatory and CMC capabilities of the IN8bio team in continuing to advance novel gamma-delta T cell therapies to cancer patients," said William Ho, Chief Executive Officer and co-founder of IN8bio. "The clinical program is designed to eventually assess DeltEx DRI with both autologous and allogeneic approaches in both the front-line and relapsed setting. We believe the insights we unlock in GBM will be essential as we apply our DeltEx platform across multiple solid tumor cancers."

The Phase 2 clinical trial will commence with the enrollment of newly diagnosed GBM patients, with the initial arm assessing autologously derived MGMT-modified gamma-delta T cells. In line with recent FDA guidance, the Company is planning to expand the trial to include an allogeneic DeltEx DRI drug product in relapsed refractory GBM and potentially the frontline setting. The primary endpoint of the study is overall survival (OS); secondary endpoints include tolerability, progression-free survival (PFS), overall response rate (ORR) and time to progression (TTP).

Conference Call Details

IN8bio will host a conference call and webcast on Monday, December 12th at 8:30 a.m. ET to review recent clinical updates, including updated data from the Phase 1 clinical trial of INB-100 being presented at ASH (Free ASH Whitepaper). The webcast can be accessed by clicking the link: View Source and can also be accessed on the Events & Presentations page of the Company’s website.

About INB-400

INB-400 is IN8bio’s DeltEx chemotherapy resistant autologous and allogeneic DRI technology. Allogeneic INB-400 will expand the application of DRI gamma-delta T cells into other solid tumor types through the development of allogeneic or "off-the-shelf" DeltEx DRI technology.

Immunocore presents ovarian cancer expansion data for ImmTAC® candidate IMC-C103C targeting MAGE-A4

On December 8, 2022 Immunocore Holdings plc (Nasdaq: IMCR), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, autoimmune and infectious diseases, reported data for IMC-C103C, a bispecific T cell engager targeting MAGE-A4, in patients with ovarian cancer (Press release, Immunocore, DEC 8, 2022, View Source [SID1234624953]).

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The Phase 1 data, presented in a poster at the ESMO (Free ESMO Whitepaper) Immuno-Oncology 2022 Congress, include 33 heavily pre-treated patients with ovarian cancer, who received doses of ≥ 90 mcg intravenously. This includes 16 new patients, and 17 patients previously reported at the ESMO (Free ESMO Whitepaper) Immuno-Oncology 2021 Congress, now with longer follow-up. All patients had platinum relapsed/refractory ovarian cancer (70% PARP inhibitors experienced) and were enrolled regardless of MAGE-A4 protein expression, which was analyzed retrospectively.

Of the 33 patients, 39% (13/33) were MAGE-A4 negative as measured by immunohistochemistry (IHC), and 2 patients had an unknown H score. Of the 55% (18/33) MAGE-A4 positive patients, the majority had low expression (median score = 29 of 300), and only 2 had an H score > 150.

The safety profile was consistent with that reported previously and the mechanism of action, i.e., T cell activation. No related AE led to treatment discontinuation or death.

At the time of data cut-off, 32 patients were evaluable for response, with one additional patient (H score 21) still on treatment and not having had first tumor assessment​. Of the 17 evaluable MAGE-A4 positive patients, one had a durable Partial Response (PR), with a duration of 12.7 months, one patient who had a Stable Disease (SD) converted to an unconfirmed PR after the poster data cutoff date and is still ongoing, and 5 had SD. Reductions in ctDNA were observed in over half of ctDNA evaluable patients (12/22), including 7 with ≥ 50% reductions, and even in those with low or zero MAGE-A4 expression.

"Immunocore has learned from tebentafusp that OS benefit and ctDNA reduction are observed in patients with both high and low total protein expression, while RECIST responses are enriched at higher protein expression," said David Berman, Head of Research and Development of Immunocore. "The emerging IMC-C103C results, where most patients had either no or very low MAGE-A4 expression, are consistent with the RECIST and ctDNA reduction results reported for tebentafusp."

IMC-C103C is part of a co-development / co-promotion collaboration with Genentech, a member of the Roche Group under which Immunocore shares program costs and profits equally. Both companies are evaluating next steps for the IMC-C103C program.

Guardant Health Announces Collaboration With AstraZeneca to Develop Companion Diagnostic to Identify Patients With ESR1-mutated Metastatic Breast Cancer

On December 8, 2022 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported that it has entered into a collaboration with AstraZeneca to pursue the development, regulatory approval and commercialization of the Guardant360 CDx blood test as a companion diagnostic to identify patients with ESR1-mutated metastatic breast cancer (Press release, Guardant Health, DEC 8, 2022, View Source [SID1234624952]). The initiative is part of a larger strategic collaboration investigating the use of liquid biopsy as a tool to inform early therapy intervention.

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The collaboration is one of the first to explore the potential of a comprehensive genomic profiling ctDNA (circulating tumor DNA) assay to identify mutation-driven resistance to a prior line of therapy in metastatic breast cancer. The Guardant360 CDx liquid biopsy test is being used to identify patients with detectable ESR1mutations in the SERENA-6 phase III clinical trial, which is evaluating camizestrant, a next-generation oral selective estrogen receptor degrader (ngSERD) being developed by AstraZeneca, in combination with CDK4/6 inhibitors versus aromatase inhibitors in combination with CDK4/6 inhibitors in patients with HR-positive, HER2-negative metastatic breast cancer.

"We’re pleased to collaborate with AstraZeneca on this important study for breast cancer patients," said Helmy Eltoukhy, Guardant Health chairman and co-CEO. "We look forward to exploring the potential benefit of early comprehensive genomic profiling using a simple blood draw, which can provide faster results than a tissue biopsy and enable clinicians to consider earlier intervention with the goal of achieving improved patient outcomes."

About Guardant Health

Guardant Health is a leading precision oncology company focused on helping conquer cancer globally through use of its proprietary tests, vast data sets and advanced analytics. The Guardant Health oncology platform leverages capabilities to drive commercial adoption, improve patient clinical outcomes and lower healthcare costs across all stages of the cancer care continuum. Guardant Health has commercially launched Guardant360, Guardant360 CDx, Guardant360 TissueNext, Guardant360 Response, and GuardantOMNI tests for advanced stage cancer patients, and Guardant Reveal for early-stage cancer patients. The Guardant Health screening portfolio, including the ShieldTM test, aims to address the needs of individuals eligible for cancer screening. For more information, visit guardanthealth.com and follow the company on LinkedIn and Twitter.

Entry Into a Material Definitive Agreement

On December 6, 2022, iBio, Inc. (the "Company") entered into an underwriting agreement (the "Underwriting Agreement") with H.C. Wainwright & Co., LLC ("Wainwright"). Pursuant to the Underwriting Agreement, the Company agreed to sell to Wainwright, in a firm commitment underwritten offering (the "Offering") (i) 1,530,769 shares of the Company’s Common Stock, par value $0.001 per share (the "Common Stock"), (ii) pre-funded warrants (the "Pre-Funded Warrants") to purchase up to 1,834,616 shares of Common Stock, (iii) Series A Common Stock purchase warrants (the "Series A Warrants") to purchase up to 3,365,385 shares of Common Stock and (iv) Series B Common Stock purchase warrants (the "Series B Warrants" and together with the Series A Warrants, the "Common Warrants") to purchase up to 3,365,385 shares of Common Stock (Filing, 8-K, iBioPharma, DEC 8, 2022, View Source [SID1234624950]).

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The combined purchase price of each share of Common Stock and the accompanying Common Stock Warrants is $1.04 and the combined purchase price of each Pre-Funded Warrant and the accompanying Common Stock Warrants is $1.039, which is equal to the combined purchase price per share of Common Stock and accompanying Common Stock Warrants, minus the exercise price of each Pre-Funded Warrant of $0.001. Each share of Common Stock and Pre-Funded Warrant, as applicable, is being sold together with one Series A Warrant to purchase one share of Common Stock and one Series B Warrant to purchase one share of Common Stock. The Series A Warrants and the Series B Warrants have an exercise price of $1.04 per share and are immediately exercisable. The Series A Warrants will expire five (5) years from the date of issuance and the Series B Warrants will expire twenty-four (24) months from the date of issuance. There is not expected to be any trading market for the Pre-Funded Warrants or the Common Stock Warrants issued in the Offering.

Pursuant to the Underwriting Agreement, the Company has granted Wainwright a 30-day option to purchase up to an additional 504,807 shares of Common Stock and/or Common Warrants to purchase up to an additional 1,009,614 shares of Common Stock at the public offering price, less the underwriting discounts and commissions, solely to cover over-allotments. The Company has also agreed to issue to Wainwright, as the representative of the underwriters, warrants (the "Representative’s Warrants") to purchase a number of shares of Common Stock equal to 6.0% of the aggregate number of shares of Common Stock and Pre-Funded Warrants being offered in the Offering at an exercise price equal to $1.30, which is 125% of the combined public offering price per share of Common Stock and the accompanying Common Stock Warrants, and to reimburse the underwriter for certain Offering-related expenses. The Representative’s Warrants may be exercised on a cashless basis if an effective registration statement is not available and will expire five years after the commencement of sales of the securities in the Offering.

The closing of the Offering is expected to occur on or about December 9, 2022, subject to the satisfaction of customary closing conditions.

The net proceeds from the Offering, after deducting underwriting discounts and commissions and other estimated offering expenses payable by the Company and excluding the net proceeds, if any, from the exercise of the Common Stock Warrants, are approximately $2.9 million (or $3.4 million if Wainwright exercises its option to purchase additional shares of Common Stock and Common Stock Warrants in full). The Company intends to use the net proceeds from the Offering primarily for operating costs, including for research and development and other trial preparation expenses in addition to working capital needs and for other general corporate purposes, which may include retention and severance payments to certain of the Company’s employees or former employees. The Company may also use a portion of the net proceeds to invest in or acquire other products, businesses or technologies, although it has no commitments or agreements with respect to any such investments or acquisitions as of the date hereof. In addition, the Company intends to use a portion of the net proceeds from the Offering to pay principal payments of $250,000 per month in debt amortization on a monthly basis through March 2023 pursuant to the terms of its amended Credit Agreement with Woodforest National Bank.

Wainwright acted as the sole book-running manager for the Offering. The Company paid Wainwright an underwriting discount equal to 7.0% of the gross proceeds of the Offering, and reimbursed Wainwright for the legal fees and certain expenses of the underwriter, in the sum of up to $100,000, in connection with this offering, up to $20,000 for certain clearance fees and settlement expenses and $25,000 for non-accountable expenses.

All securities offered and sold in the Offering (including the shares of Common Stock issuable from time to time upon exercise of the Pre-Funded Warrants, the Series A Warrants, the Series B Warrants and the Representative’s Warrants) were offered pursuant to the Company’s effective Registration Statement on Form S-3 (Registration No. 333-250973), including a base prospectus contained therein dated December 7, 2020, as supplemented by a prospectus supplement relating to the Offering, dated December 6, 2022, and filed with the Securities and Exchange Commission on the date of this Current Report on Form 8-K.

The Underwriting Agreement contains customary representations, warranties, and covenants of the Company and also provides for customary indemnification by each of the Company and Wainwright against certain liabilities and customary contribution provisions in respect of those liabilities.

The description of terms and conditions of the Underwriting Agreement does not purport to be complete and is qualified in its entirety by the full text of the Underwriting Agreement, a copy of which is attached hereto as Exhibit 1.1.

A copy of the opinion of Blank Rome LLP relating to the legality of the issuance and sale of the securities sold in the Offering is attached as Exhibit 5.1 hereto.

Terms of the Pre-Funded Warrants, Series A Warrants and Series B Warrants

The Pre-Funded Warrants were offered in lieu of shares of Common Stock to certain investors because the purchase of shares of Common Stock in the Offering would otherwise result in said investors, together with their affiliates and certain related parties, beneficially owning more than 4.99% (or, at the election of the Investor, 9.99%) of the Company’s outstanding Common Stock immediately following the consummation of the Offering. Each Pre-Funded Warrant is exercisable for one share of Common Stock at an exercise price of $0.001 per share. The Pre-Funded Warrants are immediately exercisable and may be exercised at any time until all of the Pre-Funded Warrants are exercised in full.

Each Series A Warrant and Series B Warrant offered hereby will be a Warrant to purchase one share of Common Stock and will have an initial exercise price equal to $1.04 per share. The Series A Warrants will be immediately exercisable and will expire five years from the date of issuance. The Series B Warrants will be immediately exercisable and will expire twenty-four months from the date of issuance. The exercise price and number of shares of Common Stock issuable upon exercise of the Series A Warrants and Series B Warrants is subject to appropriate adjustment in the event of share dividends, share splits, reorganizations or similar events affecting the Common Stock and the exercise price.

A holder (together with its affiliates) of the Common Stock Warrants or Pre-Funded Warrants may not exercise any portion of the Common Stock Warrants or Pre-Funded Warrants, as applicable, to the extent that the holder would own more than 4.99% (or, at the holder’s option upon issuance, 9.99%) of the Company’s outstanding Common Stock immediately after exercise, as such percentage ownership is determined in accordance with the terms of the Common Stock Warrants or Pre-Funded Warrants, as applicable. In lieu of making the cash payment otherwise contemplated to be made to the Company upon exercise of a Common Stock Warrant in payment of the aggregate exercise price, the holder may elect instead to receive upon such exercise (either in whole or in part) the net number of shares of Common Stock determined according to a formula set forth in the Common Stock Warrants, provided that such cashless exercise shall only be permitted if the Registration Statement is not effective at the time of such exercise or if the prospectus to which the Registration Statement is a part is not available for the issuance of shares of Common Stock to the Common Stock Warrant holder. In addition, in certain circumstances, upon a fundamental transaction (as defined in the Common Stock Warrants), the holder will have the right to require the Company to repurchase the Common Stock Warrants at the Black Scholes Value (as defined in the Common Stock Warrants); provided, however, that, if the fundamental transaction is not within the Company’s control, including not approved by the Company’s board of directors, then the holder shall only be entitled to receive the same type or form of consideration (and in the same proportion), at the Black Scholes Value of the unexercised portion of the Common Stock Warrants, that is being offered and paid to the holders of Common Stock of the Company in connection with the fundamental transaction.

In lieu of making the cash payment otherwise contemplated to be made to the Company upon exercise of a Pre-Funded Warrant in payment of the aggregate exercise price, the holder may elect instead to receive upon such exercise (either in whole or in part) the net number of shares of Common Stock determined according to a formula set forth in the Pre-Funded Warrants.

The description of terms and conditions of the Pre-Funded Warrants, Series A Warrants, Series B Warrants and Representative’s Warrants do not purport to be complete and are qualified in their entirety by the full text of the form of such Pre-Funded Warrants, Series A Warrants, Series B Warrants and Representative’s Warrants, copies of which are attached hereto as Exhibits 4.1, 4.2, 4.3 and 4.4, respectively.

Fresenius Kabi expands injectable oncology portfolio in the U.S.

On December 8, 2022 Fresenius Kabi reported that it has introduced Pralatrexate Injection, a drug for the treatment of relapsed or refractory peripheral T-cell lymphoma in the U.S. Fresenius Kabi Pralatrexate Injection that is a generic of Folotyn and is available to customers immediately (Press release, Fresenius, DEC 8, 2022, View Source [SID1234624949]). It is the newest addition to the company’s injectable oncology medicine portfolio, the largest in U.S. health care.

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