On June 30, 2022 (the "Effective Date"), Geron Corporation (the "Company") reported that it entered into a second amendment (the "second amendment") to the Loan and Security Agreement dated September 30, 2020, as amended (the "Loan Agreement") with Hercules Capital, Inc., as administrative agent and collateral agent (in such capacity, the "Agent") and a lender, and Silicon Valley Bank, as a lender (collectively with Hercules Capital, Inc., the "Lenders") (Filing, 8-K, Geron, JUN 30, 2022, View Source [SID1234616426]). Under the second amendment, the aggregate principal amount available to the Company increased from $75 million to $125 million (the "Term Loan"), with such principal being available in a series of tranches, subject to certain terms and conditions. As of June 30, 2022, the total outstanding principal amount under the Loan Agreement is $50 million.

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The tranches for the remaining $75 million of the Term Loan (the "Remaining Tranches") available to the Company are as follows: a) the first remaining tranche of $20 million (the "First Tranche") is available within 30 days of the achievement of certain clinical and financial milestones until September 15, 2023, subject to the achievement of such milestones; b) the second remaining tranche of $10 million is available from January 1, 2023 until December 15, 2023, subject to the achievement of certain clinical and regulatory milestones, and satisfaction of certain other requirements; c) the third remaining tranche of $20 million is available from September 15, 2023 until September 15, 2024, subject to the achievement of certain clinical and regulatory milestones, and satisfaction of certain capitalization requirements; and d) the final tranche of $25 million is available through December 31, 2024, subject to the Lenders’ approval. With the exception of the final tranche, and subject to achievement of the applicable milestones and other requirements with respect to each tranche, utilization of the Remaining Tranches under the Term Loan is at the Company’s election.

Under the second amendment, the Company is required to pay 1.0% facility charge for each of the remaining tranches that is drawn down by the Company after the Effective Date, including 0.5% of facility charge with respect to the First Tranche paid at the Effective Date. If the Company chooses to prepay the principal with respect to any Remaining Tranche drawn down after the Effective Date, any such prepayment within the first 36 months after the Effective Date will be subject to a prepayment charge equal to 1.5% of the principal amount prepaid. No prepayment charge will be assessed for any prepayment occurring more than 36 months after the Effective Date.

The maturity date, interest only payment dates, end of term charges, collateral, events of default, representations, warranties and covenants remain consistent with the terms of the original Loan Agreement, except as follows:

●Beginning June 1, 2022 and prior to the potential achievement by the Company of regulatory approval for imetelstat (the "potential Regulatory Approval"), if any, the Company is required to maintain a minimum cash balance in an amount equal to the greater of: 50% of the outstanding principal amount under the Loan Agreement or $30 million.

●After the potential Regulatory Approval, if any, the minimum cash requirement may be satisfied through one of the following three options, as elected by the Company: a) maintaining a cash balance in an amount not less than 40% of the outstanding principal amount under the Loan Agreement; b) maintaining a cash balance in an amount not less than 25% of the outstanding principal amount under the Loan Agreement, if the Company’s market cap is or exceeds $750 million; or c) maintaining six month net product revenues of at least 70% of net product revenues forecasted by the Company, should any potential Regulatory Approval for imetelstat be obtained.

The descriptions of the second amendment to the Loan Agreement contained herein do not purport to be complete and are qualified in their entirety by reference to the complete text of the second amendment to the Loan Agreement, a copy of which will be filed as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ending June 30, 2022.

On June 30, 2022 Nanostics Inc., a precision health diagnostics company, reported that positive data from a pre-biopsy clinical validation study of its ClarityDX Prostate test designed to improve the accuracy of detecting clinically significant prostate cancer in men that are at risk of the disease (Press release, Nanostics, JUN 30, 2022, View Source [SID1234616423]).

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The ClarityDX Prostate test uses a proprietary machine-learning algorithm that combines data from two biological biomarkers and three clinical biomarkers to generate a risk score for clinically significant prostate cancer. The ClarityDX Prostate test is intended to be used as a reflex test for men with elevated levels of PSA, the current prostate cancer screening test, and is designed to help physicians and patients make a more informed decision to proceed with biopsy or not.

"We are extremely excited to announce positive results from the clinical validation study of the ClarityDX Prostate test in Alberta", John Lewis, CEO of Nanostics said, "Implementing ClarityDX Prostate as a reflex test for men with elevated PSA levels will improve decision-making for men and their families, while providing substantial savings for healthcare systems and resulting in better health outcomes for men with prostate cancer."

A total of 1,437 men between 40-75 years of age, with elevated PSA levels, no prior prostate cancer diagnosis, and who were referred for prostate biopsy, were recruited for this clinical study. Algorithmic risk models to predict prostate cancer or clinically significant (grade group ≥2) prostate cancer were generated using data from 1036 men recruited at the Kipnes Urology Center in Edmonton, AB, and a site in Baltimore, USA. These models were then tested in a validation cohort of 401 men recruited at the Prostate Cancer Center in Calgary, AB.

The ClarityDX Prostate test provided 94% sensitivity, 37% specificity, 49% positive predictive value, and 90% negative predictive value for predicting clinically significant (grade group ≥2) prostate cancer. The potential impact of the ClarityDX Prostate test is considerable; implementation could eliminate up to 37% of unnecessary biopsies and significantly reduce the number of unnecessary treatments for prostate cancer. The results from the study are being submitted for peer-reviewed publication. Beyond the immediate cost savings to the healthcare system, the launch of the ClarityDX Prostate test will positively impact the overall healthcare experience and quality of life for men with prostate cancer.

The study was conducted in partnership with DynaLIFE Medical Labs and the Alberta Prostate Cancer Research Initiative (APCaRI) at the University of Alberta. Funding for the clinical study comes in part from The Bird Dogs, Motorcycle Ride for Dad, Alberta Cancer Foundation, Alberta Innovates, the University Hospital Foundation Kaye Fund, and the Frank and Carla Sojonky Chair in Prostate Cancer Research funded by the Alberta Cancer Foundation, held by Dr. John Lewis from 2012 to 2022.

On June 30, 2022 Inceptor Bio, a biotechnology company advancing cell therapies for difficult-to-treat cancers, reported a collaboration with University of Minnesota (Press release, Inceptor Bio, JUN 30, 2022, View Source [SID1234616422]). The aim of this collaboration is to build a novel induced pluripotent stem cells (iPSC) platform that will accelerate Inceptor Bio’s best-in-class next-generation cell therapies platforms. Under the terms of the agreement, Inceptor Bio will receive an exclusive license to the technology developed under this collaboration.

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Inceptor Bio plans to advance multiple cell therapy products into clinical studies incorporating the iPSC platform into its proprietary K62 platform for CAR-M therapy, which increases the phagocytic capabilities of macrophages and supports an M1 anti-tumor phenotype, as well as its novel co-stimulatory domain, M83, for CAR-NK therapies.

"iPSC-derived cell therapies have the potential to enable the next frontier of cell therapies. We are excited to work with Dr. Beau Webber at University of Minnesota and his team to develop this unique platform," said Mike Nicholson, Ph.D., President and Chief Operating Officer at Inceptor Bio.

"The team at University of Minnesota is confident that Inceptor Bio is the right partner for building a differentiated iPSC platform to advance novel cell therapies," said Beau Webber, Ph.D., Assistant Professor in the Department of Pediatrics, Division of Hematology and Oncology. "We are deeply encouraged by Inceptor Bio’s progress in the cell therapy arena, and we look forward to being part of future developments to help cure difficult-to-treat cancers."

"This partnership is an important step in continuing to execute on our strategy of advancing cell therapies to bring a more positive prognosis and quality of life to patients with difficult-to-treat cancers," said Abe Maingi, Vice President, Business Development at Inceptor Bio. "We are thrilled to be able to develop and deliver on the promise of iPSC-derived cell therapies."

On June 30, 2022 Inhibrx, Inc. (Nasdaq: INBX), a biotechnology company with four clinical programs in development and a robust preclinical pipeline, reported the completion of Phase 1 dose escalation of INBRX-105, a novel targeted 4-1BB agonist, in combination with Keytruda (Press release, Inhibrx, JUN 30, 2022, View Source [SID1234616421]). It also reported the funding of an additional $60 million from its Loan and Security Agreement, as amended (the "Loan Agreement"), with Oxford Finance, LLC ("Oxford"), to bring its cash balance to approximately $176 million as of June 30, 2022.

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"We are very encouraged by the results observed in Part 3 and believe the Part 4 expansion cohorts have been designed to demonstrate the potential of INBRX-105," commented Mark Lappe, Inhibrx’s CEO. "The additional debt provided by Oxford provides non-dilutive financing and, we believe, the time needed to mature our programs ahead of various potential strategic options."

Phase 1 Dose Escalation Results for INBRX-105 in Combination with Keytruda
INBRX-105 is a precisely engineered multi-specific therapeutic candidate based on our single domain antibody ("sdAb") platform designed to agonize 4-1BB selectively in the presence of programmed death ligand 1 ("PD-L1"), a protein typically enriched in the tumor microenvironment and lymphoid tissues.

The study is a first-in-human, multicenter, open-label, non-randomized, Phase 1 trial in patients with locally advanced or metastatic solid tumors. This four-part trial is designed to determine the safety profile and identify the maximum tolerated dose and the recommended Phase 2 dose of INBRX-105 administered in combination with Keytruda, a programmed death receptor-1 checkpoint inhibitor. Part 3, dose escalation in combination with Keytruda, has concluded with a total of 30 patients enrolled. Patients were not pre-screened for PD-L1 expression. INBRX-105 in combination with Keytruda was reasonably well-tolerated and we observed durable responses in checkpoint-naïve and relapsed refractory patients. These results informed what we believe to be the optimal dose level for INBRX-105 in combination with Keytruda in Part 4. Additionally, single agent responses have been observed at this same dose level in both checkpoint-naïve and relapsed/refractory patients.

Part 4, dose expansion cohorts of INBRX-105 in combination with Keytruda, initiated enrollment in May 2022. This will include a total of approximately 90 patients in five separate cohorts and we expect to announce initial data from these cohorts in the first half of 2023.

Additional $60 Million in Debt from Oxford
On June 29, 2022, Inhibrx drew two additional term loans from its Loan Agreement with Oxford for an aggregate principal amount of $60.0 million. The two additional term loans were based on the completion of the following:

$30 million upon the receipt of positive topline data from the Phase 1 clinical trial of INBRX-101, our AAT-Fc fusion protein for the treatment of Alpha-1 antitrypsin deficiency, which we released in May 2022; and
$30 million upon initiation of Part 4 of the Phase 1 clinical trial of INBRX-105, our PD-L1x4-1BB tetravalent conditional agonist.
Inhibrx has one additional $30 million tranche available under the Loan Agreement, which will be available to fund upon the initiation of a potential registration-enabling clinical trial of INBRX-101. To date, the aggregate balance of Inhibrx’s outstanding term loans, which mature in January 2027, is $170.0 million. The repayment schedule provides for interest-only payments until March 2025 with a potential 12-month extension.

On June 30, 2022 Insightec, a global healthcare company dedicated to using acoustic energy to transform patient care, reported that it has received FDA approval for an investigational device exemption (IDE) for a clinical comparative study of the Exablate Prostate system used to treat diseased prostate tissue (Press release, Insightec , JUN 30, 2022, View Source [SID1234616420]). This study will evaluate the safety and efficacy of focal treatment using high intensity focused ultrasound when compared to active surveillance in men living with prostate cancer.

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The Insightec Exablate Prostate system uses sound waves to ablate, or destroy, targeted tissue in the prostate. The treatment is performed under Magnetic Resonance Imaging (MRI) guidance for high resolution visualization of the patient’s anatomy for precise targeting and real-time temperature monitoring. The single session treatment does not require incisions and allows patients to quickly return to normal activity with minimal complications.

"We are excited to continue this important research that can impact on the standard of care for prostate cancer treatment," said Behfar Ehdaie, MD, MS, a urologic surgeon at Memorial Sloan Kettering Cancer Center, and principal investigator for the study. "Exablate Focused Ultrasound has been shown to provide an accurate, safe, and effective option to engage the prostate gland directly in select patients based on 2-years biopsy outcomes. The new trial will build on this success and help further enhance treatment options."

"At Insightec, we are committed to the next generation of prostate cancer research and patient care," said Maurice R. Ferré, MD, Insightec CEO and Chairman of the Board. "Through technological innovation and medical advancements, there has been significant progress made in treating the prostate over the last decade, but we’re not done yet. Our goal for this study is to demonstrate the clinical benefits of Exablate Prostate and provide patients with the opportunity for improved quality of life outcomes."

A previous Insightec-sponsored clinical trial led by Memorial Sloan Kettering Cancer Center for the Exablate Prostate system reported minimal damage to adjacent structures and low rates of impact on potency and continence, supporting function and quality of life for patients. The new comparative study builds on the evidence of this clinical trial and aims to further enhance prostate treatment options and improve clinical outcomes.

The Insightec Exablate Prostate system received 510(k) FDA clearance in November 2021, making way for the system to be offered to patients in a commercial facility and for further clinical studies. In January 2022, the system was used to treat prostate disease in its first US commercial patient.

Results from the new study will define the role of focal therapy to delay and avoid radical therapy for men with prostate cancer and support expanded clinical adoption of the technology and increased access for patients through insurance reimbursement.