Genentech provides update on Gavreto U.S. indication for advanced or metastatic medullary thyroid cancer

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Entry into a Material Definitive Agreement

On June 29, 2023, CytomX Therapeutics, Inc. (the "Company") reported to have entered into a unit purchase agreement (the "Purchase Agreement") with certain accredited investors (the "Purchasers") (Filing, CytomX Therapeutics, JUN 29, 2023, View Source [SID1234633030]). The Purchase Agreement provides for the sale and issuance by the Company of an aggregate of: (i) pre-funded warrants (the "Pre-Funded Warrants") to purchase up to 14,423,077 shares of the Company’s common stock, $0.00001 par value per share (the "Common Stock"), (ii) Tranche 1 Warrants (the "Tranche 1 Warrants") to purchase up to 5,769,231 shares of Common Stock (or Pre-Funded Warrants in lieu thereof) and (iii) Tranche 2 Warrants (the "Tranche 2 Warrants" and collectively with the Tranche 1 Warrants, the "Tranche Warrants", and further, the Tranche Warrants collectively with the Pre-Funded Warrants, the "Securities") to purchase up to 5,769,231 shares of Common Stock (or Pre-Funded Warrants in lieu thereof) (collectively, the "Private Placement"). The combined price per Pre-Funded Warrant and accompanying Tranche Warrants is $2.08. The Pre-Funded Warrants are immediately exercisable at an exercise price of $0.00001 per share and have a term of 20 years. The Pre-Funded Warrants and the Tranche Warrants are immediately separable and were issued separately. The closing of the Private Placement is expected to occur on July 3, 2023 (the "Closing"), subject to the satisfaction of customary closing conditions.

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A holder (together with its affiliates) may not exercise any portion of a Pre-Funded Warrant or Tranche Warrant to the extent that the holder would own more than 9.99% of the Company’s Common Stock outstanding immediately after exercise. However, upon at least 61 days’ prior notice from the holder to the Company, a holder with a 9.99% ownership blocker may increase or decrease the amount of ownership of outstanding Common Stock after exercising the holder’s Warrant up to 19.99% of the Company’s Common Stock outstanding immediately after giving effect to the exercise, as such percentage ownership is determined in accordance with the terms of the Pre-Funded Warrants and Tranche Warrants.

The Tranche Warrants are immediately exercisable. Each Tranche 1 Warrant has an initial exercise price of $4.16 per share of Common Stock and each Tranche 2 Warrant has an initial exercise price of $6.24 per share of Common Stock, in each case subject to certain adjustments. The Tranche 1 Warrants expire on July 3, 2025 and the Tranche 2 Warrants expire on July 3, 2026.

If, prior to the expiration date of either the Tranche 1 Warrants or Tranche 2 Warrants, the Company sells shares of Common Stock or derivative securities convertible into or exercisable for Common Stock (other than Exempted Securities as defined in the Tranche Warrant) in one or more related transactions primarily for the purpose of raising capital at a Weighted-Average Price (as described below) below the exercise price of $4.16, then the initial exercise price of both the Tranche 1 Warrants and Tranche 2 Warrants will be automatically reset upon exercise to an exercise price (the "Adjusted Exercise Price") that is the midpoint between the initial exercise price of the Tranche 1 Warrant and the Tranche 2 Warrant, as applicable, and the lowest Weighted-Average Price per share at which the Company sells shares of Common Stock or derivative securities convertible into or exercisable for Common Stock in such subsequent offering prior to the exercise date; provided, that the Adjusted Exercise Price will not be reduced below $2.08 per share. The Weighted-Average Price shall be calculated as the weighted-average common stock equivalent price of the equity securities sold in such transaction(s) (excluding any derivative securities with an exercise or conversion price that is above the closing sale price as of the time of pricing such offering(s)). In no event will the exercise price for the Tranche Warrants be adjusted more than once pursuant to this adjustment mechanism.

The exercise price and the number of shares of Common Stock issuable upon the exercise of the Pre-Funded Warrants and the Tranche Warrants are subject to adjustment upon the occurrence of specific events, including stock dividends, stock splits, reclassifications and combinations of the Company’s Common Stock.

The aggregate gross proceeds to the Company from this offering are approximately $30.0 million, excluding any proceeds the Company may receive upon exercise of the Tranche Warrants and the Pre-Funded Warrants. No underwriter or placement agent participated in the offering.

The Purchase Agreement contains customary representations, warranties and agreements by the Company, customary conditions to Closing and indemnification obligations of the Company and the Purchasers. The representations, warranties and covenants contained in the Purchase Agreements were made only for purposes of such agreements and as of specific dates, were solely for the benefit of the parties to such agreements, and may be subject to limitations agreed upon by the contracting parties.

The Company has agreed to file a resale registration statement with the Securities and Exchange Commission on or before the date that is 60 calendar days after the Closing, to register the resale of the shares of Common Stock issuable upon exercise of the Pre-Funded Warrants and the Tranche Warrants. The foregoing description of the Purchase Agreement, Pre-Funded Warrants and Tranche Warrants is not complete and is qualified in its entirety by reference to the full text of the Purchase Agreement, form of Pre-Funded Warrant and form of Tranche Warrant, which are filed as Exhibits 10.1, 4.1 and 4.2, respectively, to this Current Report on Form 8-K and incorporated by reference herein.

Entry into a Material Definitive Agreement

On June 29, 2023, Black Diamond Therapeutics, Inc. (the "Company") reorted to have entered into an underwriting agreement (the "Underwriting Agreement") with Piper Sandler & Co., as representative of the several underwriters named in Schedule 1 thereto (collectively, the "Underwriters"), pursuant to which the Company agreed to issue and sell up to 15,000,000 shares (the "Shares") of common stock, par value $0.0001 per share (the "common stock") in an underwritten public offering (the "Offering") (Filing, 8-K, Black Diamond Therapeutics, JUN 29, 2023, View Source [SID1234633003]). The Shares were offered and sold in the Offering at the public offering price of $5.00 per share and were purchased by the Underwriters from the Company at a price of $4.70 per share. Under the terms of the Underwriting Agreement, the Company also granted to the Underwriters an option, exercisable in whole or in part at any time for a period of 30 days from the date of the Underwriting Agreement, to purchase up to an additional 2,250,000 shares of common stock at the public offering price (the "Optional Shares").

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The Offering is being made pursuant to the Company’s effective registration statement on Form S-3 (Registration No. 333-268341), which was previously filed with the Securities and Exchange Commission (the "SEC") on November 14, 2022 and declared effective by the SEC on November 22, 2022, a base prospectus dated November 14, 2022 and a prospectus supplement dated June 29, 2023.

The Company estimates that the net proceeds from the Offering, after deducting the underwriting discounts, commissions and reimbursements and estimated offering expenses payable by the Company, will be approximately $71.6 million, or approximately $82.4 million if the Underwriters exercise in full their option to purchase the Optional Shares. The Company intends to use the net proceeds from the offering for the advancement of the Company’s clinical development pipeline, including potential accelerated approval activities for BDTX-1535 in non-small cell lung cancer, as well as for working capital, and general corporate purposes. The Offering is expected to close on July 5, 2023, subject to customary closing conditions.

The Underwriting Agreement contains customary representations, warranties and covenants made by the Company. The Company also agreed to indemnify the Underwriters against certain liabilities, including liabilities under the Securities Act of 1933, as amended, or to contribute to payments that the Underwriters may be required to make because of such liabilities.

Pursuant to the Underwriting Agreement, the Company’s executive officers and directors entered into lock-up agreements in substantially the form included as an exhibit to the Underwriting Agreement, providing for a 60-day "lock-up" period with respect to sales of common stock, subject to certain exceptions.

The foregoing is a summary description of the Underwriting Agreement and is qualified in its entirety by the text of the Underwriting Agreement attached as Exhibit 1.1 to this Current Report on Form 8-K and incorporated herein by reference.

A copy of the opinion of Goodwin Procter LLP relating to the validity of the Shares issued in the Offering is filed herewith as Exhibit 5.1.

TME Pharma Announces Positive 15-month Survival Data From GLORIA Expansion Arm Evaluating NOX-A12 in Combination With Radiotherapy and Bevacizumab in Glioblastoma

On June 29, 2023 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported a positive clinical update on the survival of first-line glioblastoma patients in the GLORIA expansion arm evaluating NOX-A12, TME Pharma’s CXCL12 inhibitor, in combination with standard of care radiotherapy and anti-VEGF, bevacizumab (Press release, TME Pharma, JUN 29, 2023, View Source [SID1234632996]).

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After 15 months on study (median), 83% of GLORIA expansion arm patients (5 of 6) remain alive. As long as treatment or follow-up for these patients is ongoing, median overall survival (mOS) will continue to improve1. As a reference, the expected median overall survival for patients under current standard of care with chemotherapy refractory tumors (MGMT unmethylated) and whose tumor remains detectable after surgical intervention is approximately 10 months2.

"Reaching the 15-month survival point with this expansion arm is a significant milestone in our development of NOX-A12 in glioblastoma, and to do so with more than 80 percent of patients still on study represents a fantastic achievement," said Aram Mangasarian, CEO of TME Pharma. "This latest set of survival data further underlines the clinically meaningful improvement that this treatment combination of NOX-A12, radiotherapy and bevacizumab could bring over the current standard of care for this challenging indication with extremely poor prognosis. We are building an enviable clinical profile around our lead asset in glioblastoma, which strengthens NOX-A12’s position for potential partnering and our coming discussions with regulators regarding the pathway to market."

Blue Earth Therapeutics Announces Results of Early Clinical and Preclinical Studies of Investigational 177Lu-rhPSMA-10.1 in Treatment of Prostate Cancer

On June 29, 2023 Blue Earth Therapeutics, a Bracco company and emerging leader in the development of innovative next generation therapeutic radiopharmaceuticals, reported highlights from early clinical and preclinical studies of 177Lu-rhPSMA-10.1 by the Company and a collaborator at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, June 24 – 27, 2023 (Press release, Blue Earth Therapeutics, JUN 29, 2023, View Source [SID1234632995]). 177Lu-rhPSMA-10.1 is an investigational radiohybrid (rh) Prostate-Specific Membrane Antigen-targeted therapeutic radiopharmaceutical for the treatment of prostate cancer. The presentations included results from an independent clinical study conducted by the University of Augsburg that investigated dosimetry and the therapeutic index for 177Lu-rhPSMA-10.1. Also being presented are results of Blue Earth Therapeutics’ preclinical studies that examined the therapeutic dose response of 177Lu-rhPSMA-10.1 and the therapeutic efficacy of 177Lu-rhPSMA-10.1 as compared to several other compounds. 177Lu-rhPSMA-10.1 is the first clinical candidate in Blue Earth Therapeutics’ oncology development program of advanced targeted therapeutic radiopharmaceuticals. An investigational Phase 1/2 clinical trial (NCT05413850) evaluating the safety, tolerability, dosimetry and anti-tumor activity of 177Lu-rhPSMA-10.1 in eligible men with metastatic castrate-resistant prostate cancer (mCRPC) is underway in the United States.

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"We are pleased to share these initial results from Blue Earth Therapeutics’ rhPSMA-10.1 program in prostate cancer with the nuclear medicine community at the SNMMI 2023 Annual Meeting," said David E. Gauden, D.Phil., Chief Executive Officer of the Company. "Our goal at Blue Earth Therapeutics is to deliver precise, targeted therapy specific to the patient’s condition. The radiohybrid PSMA theranostic technology platform enables molecules within the class to be modified and deployed for either diagnostic PET imaging or therapeutic applications, and can also be developed with both beta- and alpha-emitting therapeutic radioisotopes. Our lead therapeutic compound, 177Lu-rhPSMA-10.1, was carefully optimized during development with the aim of maximizing its therapeutic index by delivering high radiation doses to prostate cancer lesions while sparing normal tissues as far as possible. The preclinical efficacy results in prostate cancer xenografts reported here support a promising therapeutic profile for 177Lu-rhPSMA-10.1. They are further supported by the early clinical experience of our collaborators in Augsburg, where the team observed an average 3.3-fold higher tumor absorbed radiation dose compared to PSMA-I&T in a direct intra-patient comparison, without a proportional increase in radiation dose to the kidney."

Highlights of the presentations

Improved therapeutic index with the novel PSMA-ligand 177Lu-rhPSMA-10.1 compared to 177Lu-PSMA I&T – an intrapatient comparison

Results from an independent clinical study by BET collaborators at University Hospital Augsburg, Augsburg, Germany, were presented by Ralph Bundschuh, MD, PhD, Nuclear Medicine, Faculty of Medicine. The study was designed to evaluate and compare dosimetry and therapeutic indices for 177Lu-rhPSMA-10.1 and 177Lu-PSMA I&T. It included 4 patients with advanced, histologically confirmed metastatic castrate resistant prostate cancer, each patient received 177Lu-rhPSMA-10.1 (1.06 ± 0.05 GBq) and 177Lu-PSMA-I&T (1.09 ± 0.02 GBq), within 2 subsequent weeks. Dosimetry studies were performed to assess whole body uptake as well as, more specifically, uptake in salivary glands, kidneys, liver, spleen, bone marrow and up to 4 tumor lesions. The therapeutic index (TI), the ratio between mean dose to the metastases and the mean dose to the kidneys, was calculated for each patient.

The effective whole-body dose was found to be (0.038 ± 0.008) Sv/GBq for 177Lu-rhPSMA-10.1 and thus higher than for 177Lu-PSMA-I&T (0.022 ± 0.005) Sv/GBq, mainly due to 50% higher dose to the kidneys with (0.69 ± 0.30) Gy/GBq for 177Lu-rhPSMA-10.1 vs. (0.46 ± 0.11) Gy/GBq for 177Lu-PSMA-I&T. Bone marrow doses were (0.07 ± 0.06) Gy/GBq for 177Lu-rhPSMA-10.1 vs. (0.04 ± 0.04) Gy/GBq for 177Lu-PSMA-I&T, while doses to the salivary glands were (0.43 ± 0.18) Gy/GBq for 177Lu-rhPSMA-10.1 vs. (0.13 ± 0.04) Gy/GBq for 177Lu-PSMA-I&T. Tumor doses were significantly higher with 177Lu-rhPSMA-10.1 than 177Lu-PSMA-I&T. Across each evaluated lesion, 177Lu-rhPSMA-10.1 delivered an average of 3.3 times (1.2-8.3) higher tumor absorbed radiation dose. The TI was higher for 177Lu-rhPSMA-10.1 compared with 177Lu-PSMA-I&T (Patient 1, 43%, Patient 2, 213%, Patient 3, 70%, Patient 4, 6.4%) in all cases. Based on these initial results, the use of 177Lu-rhPSMA-10.1 has the potential to increase the tumor absorbed dose and improve the TI. An improved TI gives the option of maximizing tumor absorbed radiation doses, or, in earlier disease, reducing the radiation exposure to normal organs while still achieving an effective tumor dose. They noted that careful assessment of kidney and salivary gland organ function in prospective clinical trials is necessary.

Enhanced therapeutic response to 177Lu-rhPSMA-10.1 in preclinical models of prostate cancer

Caroline Foxton, Ph.D., Blue Earth Therapeutics, Oxford, UK, presented data from preclinical models of prostate cancer designed to evaluate the therapeutic response to 177Lu-rhPSMA-10.1 using several radiation dose levels, and compare the efficacy of 177Lu-rhPSMA-10.1 to 177Lu-PSMA-617 and 177Lu-PSMA-I&T. Results showed that in LNCaP xenografts a single dose of 177Lu-rhPSMA-10.1 significantly suppressed tumor growth (from day 11, p<0.05, to day 32, p<0.0001) and prolonged survival (p=0.001) at all doses tested (15, 30 or 45MBq) compared with controls. Tumor growth was significantly reduced with 30 MBq and 45 MBq compared with 15 MBq of 177Lu-rhPSMA-10.1 (from day 35, p=0.001, to day 49, p<0.0001), suggesting a dose-response effect. Median survival was 28 days for vehicle control and was not reached for the 177Lu-rhPSMA-10.1 groups at the study endpoint and all dose levels of 177Lu-rhPSMA-10.1 were well-tolerated.

In 22Rv1 xenografts, both 177Lu-rhPSMA-10.1 and 177Lu-PSMA-617 significantly suppressed tumor growth (from day 18 onwards, p<0.05, to day 35, p<0.0001) and prolonged survival (p≤0.01) compared with vehicle control. 177Lu-PSMA-I&T inhibited tumor growth to a lesser extent (from day 25 onwards, p<0.05, to day 35, p<0.0001). When compared with 177Lu-PSMA-I&T, 177Lu-rhPSMA-10.1 significantly reduced tumor growth from day 32 onwards (p<0.05) to day 49 (p<0.0001), whereas 177Lu-PSMA-617 significantly reduced tumor growth on day 49 only (p<0.05). Median survival was 33.5 days for vehicle control, 44 days for 177Lu-PSMA-I&T and was not reached for the 177Lu-rhPSMA-10.1 and 177Lu-PSMA-617 groups. All treatments were well-tolerated. The authors concluded that the analyses demonstrate significant therapeutic efficacy with 177Lu-rhPSMA-10.1 in prostate cancer xenografts, at clinically and sub-clinically equivalent dose levels. They noted that the promising therapeutic profile observed for 177Lu-rhPSMA-10.1 compared with 177Lu-PSMA-617 and 177Lu-PSMA-I&T further supports its clinical development.

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, which can 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 PSMA 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.