On August 9, 2023 Delcath Systems, Inc. (Nasdaq: DCTH) ("Delcath" or the "Company"), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported business highlights and financial results for the second quarter ended June 30, 2023 (Press release, Delcath Systems, AUG 9, 2023, View Source [SID1234634065]).

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Recent Business Highlights
During and since the second quarter, Delcath:
•Has continued to communicate with the United States Food and Drug Administration (FDA) as the agency continues its review of the HEPZATO KIT New Drug Application (NDA) resubmission with an anticipated PDUFA date of August 14, 2023;

•Received stockholders approval for the potential issuance in excess of 19.99% of Delcath’s outstanding common stock upon the conversion of the preferred stock issued pursuant to a private placement that closed on March 29, 2023 and generated $25 million on closing with up to an additional $35 million expected upon the exercise of warrants into additional series of preferred stock upon the approval of the HEPZATO KIT NDA and up to an additional $25 million upon the achievement of $10 million in quarterly revenue;

•Hired Vojislav Vukovic, MD, PhD as Chief Medical Officer; Sandra Pennell as Senior Vice President of Finance; and Zac MacLean as Director of Sales and Strategy; and

•Continued to treat patients at 3 Expanded Access Program sites.

"As we approach the August 14 PDUFA date, the Company has been preparing for the commercialization of HEPZATO KIT, if approved," said Gerard Michel, Chief Executive Officer of Delcath. Mr. Michel added, "As part of this preparation, we continue to add experienced personnel across the key functional areas involved in commercialization."
Delcath will schedule an update call shortly after the FDA’s action on the HEPZATO KIT NDA resubmission, which the Company expects to occur on or around the anticipated PDUFA date of August 14, 2023.

Second Quarter 2023 Results

Financial Highlights.

Total revenue for the three months ended June 30, 2023, was approximately $0.5 million, compared to $0.8 million for the prior year period, from our sales of CHEMOSAT in Europe. This decrease in product revenue is primarily due to potential commercial patients in the Netherlands being treated in the CHOPIN trial and reduced demand in Germany, possibly due to tebentefusp usage.

Research and development expenses for the quarter were $3.6 million, compared to $5.6 million in the prior year quarter. The decrease in R&D expense is primarily due to completing clinical trial activities. The prior year quarter included expenses for the preparation of the pre-NDA meeting with the FDA. Selling, general and administrative expenses for the quarter increased to $4.8 million, compared to $4.5 million in the prior year quarter primarily relating to activities to prepare for a commercial launch if the HEPZATO KIT is approved.

On August 9, 2023 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, reported financial results for the second quarter ended June 30, 2023 and provided a corporate update (Press release, Deciphera Pharmaceuticals, AUG 9, 2023, View Source [SID1234634063]).

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"QINLOCK delivered record performance in the second quarter based on continued growth in the U.S. and around the world. Moving into a significant second half of 2023, we are looking forward to the top-line results from the MOTION study of vimseltinib in patients with tenosynovial giant cell tumor (TGCT), which has the potential to become our second approved medicine," said Steve Hoerter, President and Chief Executive Officer of Deciphera Pharmaceuticals. "Additionally, we have opened the first sites for INSIGHT, the pivotal Phase 3 study of QINLOCK versus sunitinib in second-line gastrointestinal stromal tumor (GIST) patients with mutations in KIT exon 11 and 17 or 18 and for additional combination cohorts of our ULK inhibitor DCC-3116, one in combination with QINLOCK and another in combination with encorafenib and cetuximab. We are on track to submit an Investigational New Drug application to the FDA for DCC-3084, a potential best-in-class pan-RAF inhibitor, in the fourth quarter."

Mr. Hoerter continued, "We are proud of the significant progress across both our early-stage and late-stage programs that we have already achieved in the first half of 2023. In addition to the INTRIGUE Phase 3 ctDNA analysis presented at the ASCO (Free ASCO Whitepaper) Plenary Session in the first quarter, we also presented eight poster presentations at AACR (Free AACR Whitepaper) that showcased the depth and breadth of our kinase switch-control research engine along with the nomination of our newest development candidate, DCC-3009, a potential best-in-class pan-KIT inhibitor. At ASCO (Free ASCO Whitepaper) in June, we had one encore presentation of our INTRIGUE Phase 3 ctDNA analysis and three poster presentations, including overall survival and long-term safety data from the INTRIGUE Phase 3 study of QINLOCK. Finally, on behalf of everyone at Deciphera, I would like to thank Dan Flynn for his dedication to Deciphera’s founding vision of improving the lives of people with cancer, and for trailblazing the innovations that have made all these advancements possible. We are excited to build upon this foundation with Dash Dhanak as our new Chief Scientific Officer."

Second Quarter 2023 Highlights and Upcoming Milestones

QINLOCK (ripretinib)

Recorded $37.3 million in QINLOCK net product revenue in the second quarter of 2023, including $28.9 million in U.S. net product revenue and $8.4 million in international net product revenue, an increase of 18% compared to net product revenue of $31.5 million in the second quarter of 2022. In addition, QINLOCK generated $1.0 million in collaboration revenue driven by royalties for sales of QINLOCK by Zai Lab, the Company’s partner in Greater China.
Presented one encore presentation and three poster presentations at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting featuring an update from the ASCO (Free ASCO Whitepaper) Plenary Series Session presenting circulating tumor DNA (ctDNA) analysis results from the INTRIGUE Phase 3 study of QINLOCK, updated overall survival (OS) and long-term safety results, and outcome data on patients without detectable ctDNA at baseline from the INTRIGUE Phase 3 study of QINLOCK in patients with advanced GIST previously treated with imatinib, and information on the study design for the upcoming INSIGHT pivotal Phase 3 study of QINLOCK versus sunitinib in second-line GIST patients with KIT exon 11 and 17/18 mutations.
Initiated the INSIGHT Phase 3 study by opening the first sites for enrollment comparing QINLOCK versus sunitinib in second-line GIST patients with mutations in KIT exon 11 and 17/18.
Completed reimbursement negotiations process in Italy; launch expected shortly. Completed negotiations with the pan-Canadian Pharmaceutical Alliance (pCPA) in April 2023, which will enable broad access to fourth-line GIST patients in Canada.
Received regulatory approval for QINLOCK in Singapore in May 2023.
Vimseltinib

Expects to announce top-line results from the MOTION pivotal Phase 3 study of vimseltinib, an investigational, orally administered, potent, and highly selective switch-control kinase inhibitor of CSF1R for the potential treatment of tenosynovial giant cell tumor (TGCT) in the fourth quarter of 2023.
Expects to present updated data from the Phase 1/2 study of vimseltinib in the fourth quarter of 2023.
DCC-3116

Presented preclinical data on combinations with DCC-3116, an investigational, orally administered, selective, and potent switch-control kinase inhibitor of ULK1/2-mediated autophagy, at the American Association for Cancer (AACR) (Free AACR Whitepaper) Annual Meeting 2023, including preclinical models in combination with QINLOCK in GIST models and with encorafenib and cetuximab in colorectal cancer (CRC) models.
Completed the Phase 1 single agent dose escalation (n=28) of DCC-3116 at doses from 50 mg – 300 mg BID; no maximum tolerated dose was reached with one dose limiting toxicity (DLT) observed (Grade 3 increased ALT at 100 mg BID) and no treatment-related serious adverse events observed.
As of August 4, 2023, combination dose escalations of DCC-3116 are ongoing with MEK inhibitors trametinib (n=11) and binimetinib (n=10), and with KRAS G12C inhibitor, sotorasib (n=6) in patients with advanced solid tumors. Evaluation of trametinib and binimetinib cohorts in combination with 50 mg QD of DCC-3116 is ongoing after dose reduction from 50 mg BID based on observed DLTs for the trametinib combination (Grade 3 skin rash and diarrhea in one patient and Grade 3 diarrhea in one patient) and the binimetinib combination (Grade 3 decreased ejection fraction in one patient and Grade 2 blurred vision in one patient).
Evaluation of sotorasib cohort in combination with 200 mg QD of DCC-3116 is ongoing; combination of sotorasib and DCC-3116 at 50 mg BID was well tolerated with no DLTs observed in three evaluable patients.
Initiated new combination escalation cohorts with the first site open for enrollment evaluating DCC-3116 (100 mg QD starting dose) in combination with QINLOCK in patients with GIST and in combination with encorafenib and cetuximab in patients with CRC. Under the terms of the clinical trial collaboration and supply agreement with Pfizer, Inc., Deciphera will sponsor the study and Pfizer will supply encorafenib at no cost.
DCC-3084

Presented preclinical data for DCC-3084, a pan-RAF inhibitor, at the AACR (Free AACR Whitepaper) Annual Meeting 2023, which demonstrated a potential best-in-class profile based on its inhibition of Class I, II, and III BRAF mutations, and BRAF fusions, and optimized pharmaceutical properties.
Expects to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for DCC-3084 in the fourth quarter of 2023.
DCC-3009

Presented preclinical data for DCC-3009, a potential best-in-class pan-KIT inhibitor, at the AACR (Free AACR Whitepaper) Annual Meeting 2023, which demonstrated its ability to potently and selectively inhibit the broad spectrum of known primary and secondary drug-resistant mutations in GIST models, spanning KIT exons 9, 11, 13, 14, 17, and 18.
Expects to submit an IND to the FDA for DCC-3009 in the first half of 2024.
Kinase Switch-Control Research Engine

Presented new preclinical data in eight poster presentations at the AACR (Free AACR Whitepaper) Annual Meeting 2023 from development candidates DCC-3116 (ULK), DCC-3084 (pan-RAF), DCC-3009 (pan-KIT) and research programs focused on GCN2 and PERK, novel targets in the integrated stress response pathway.
Corporate Update

Announced that the Company’s Founder, Executive Vice President, and Chief Scientific Officer, Daniel L. Flynn, Ph.D., will retire effective September 5, 2023, and will transition to a role as Senior Advisor to the Company. Dashyant Dhanak, Ph.D., has been appointed Executive Vice President and Chief Scientific Officer effective September 5, 2023. Dr. Dhanak brings over 30 years of experience in pharmaceutical research and discovery including most recently as Executive Vice President and Chief Scientific Officer at Incyte Corporation.
Announced that Ron Squarer has been appointed Chairperson of the Board of Directors. Mr. Squarer has over 30 years of experience in the pharmaceutical and biotechnology industry and joined Deciphera as a Director in December 2019. James A. Bristol, Ph.D., who has served as either Chairperson or Co-Chairperson since 2007, will remain a Board member of Deciphera.
Second Quarter 2023 Financial Results

Revenue: Total revenue for the second quarter of 2023 was $38.3 million, which includes $37.3 million of net product revenue of QINLOCK and $1.0 million of collaboration revenue compared to $32.5 million of total revenue, including $31.5 million of net product revenue of QINLOCK and $1.0 million of collaboration revenue, for the same period in 2022.
Cost of Sales: Cost of sales were $0.2 million in the second quarter of 2023 compared to cost of sales of $1.8 million for the second quarter of 2022. In the third quarter of 2022, Deciphera completed the sale of zero cost inventories of QINLOCK that had been expensed prior to FDA approval.
R&D Expenses: Research and development expenses for the second quarter of 2023 were $58.3 million, compared to $44.9 million for the same period in 2022. The increase was primarily due to an increase in clinical study costs related to the Phase 1/2 study of DCC-3116, the MOTION Phase 3 study and Phase 1 /2 study of vimseltinib, and clinical study costs for QINLOCK. Non-cash, stock-based compensation was $5.7 million and $5.4 million for the second quarters of 2023 and 2022, respectively.
SG&A Expenses: Selling, general, and administrative expenses for the second quarter of 2023 were $32.6 million, compared to $29.6 million for the same period in 2022. The increase was primarily due to an increase in professional, consulting, and other expenses as well as personnel-related costs. Non-cash, stock-based compensation was $7.1 million and $7.6 million for the second quarters of 2023 and 2022, respectively.
Net Loss: For the second quarter of 2023, Deciphera reported a net loss of $48.6 million, or $0.57 per share, compared with a net loss of $43.1 million, or $0.60 per share, for the same period in 2022.
Cash Position: As of June 30, 2023, cash, cash equivalents, and marketable securities were $389.4 million, compared to $426.3 million as of March 31, 2023. Based on its current operating plans, Deciphera expects its current cash, cash equivalents, and marketable securities together with anticipated product, royalty, and supply revenues, but excluding any potential future milestone payments under its collaboration or license agreements, will enable the Company to fund its operating and capital expenditures into 2026.
Conference Call and Webcast

Deciphera will host a conference call and webcast to discuss this announcement today, August 9, 2023, at 8:00 AM ET. The conference call may be accessed via this link: https://register.vevent.com/register/BI74ff2d04fe8541f48da1cf0ad35339ae. A live webcast of the conference call will be available in the "Events and Presentations" page in the "Investors & News" section of the Company’s website at View Source A replay will be available on the Company’s website approximately two hours after the conference call and will be available for 30 days following the call.

On August 9, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Decibel Therapeutics, Inc. (NASDAQ: DBTX), a clinical-stage biotechnology company dedicated to discovering and developing transformative treatments to restore and improve hearing and balance, reported a definitive agreement for the acquisition of Decibel by Regeneron at a price of $4.00 per share of Decibel common stock payable in cash at closing, with an additional non-tradeable contingent value right (CVR) to receive up to $3.50 per share in cash upon achievement of certain clinical development and regulatory milestones for Decibel’s lead investigational candidate, DB-OTO, within specified time periods (Press release, Decibel Therapeutics, AUG 9, 2023, View Source [SID1234634061]). The proposed acquisition values Decibel at a total equity value of approximately $109 million based on the amount payable at closing, and a total equity value of up to approximately $213 million if the CVR milestones are achieved.

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"We at Decibel are deeply committed to discovering and advancing innovative new therapies with the potential to be transformative for people with severe forms of hearing loss. We have built a pipeline of gene therapy product candidates for the ear that we believe have such potential. After full consideration, the Decibel Board has determined that this transaction is the best way to maximize shareholder value and ultimately benefit patients," said Laurence E. Reid, Ph.D., President and Chief Executive Officer of Decibel. "We have collaborated with our colleagues at Regeneron for the past six years and have huge respect for their research and development capabilities. We have full confidence that with Regeneron’s expertise and resources the Decibel pipeline can be optimally developed, and our team is committed to enabling that long-term success."

Decibel and Regeneron established their initial collaboration in 2017, with an extension announced in 2021, and are developing three gene therapy programs targeting different forms of congenital, monogenic hearing loss. DB-OTO, which is currently in the global Phase 1/2 CHORDTM clinical trial, is an investigational cell-selective, adeno-associated virus (AAV) gene therapy designed to provide durable, physiological hearing to individuals with profound, congenital hearing loss caused by mutations of the otoferlin gene. Preclinical programs include AAV.103 for people with GJB2-related hearing loss and AAV.104 for people with stereocilin (STRC)-related hearing loss.

"We are delighted to announce the planned acquisition of Decibel, who have been long-standing collaborators, notable for their deep scientific knowledge and commitment to people with hearing loss," said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, Chief Scientific Officer and President of Regeneron. "DB-OTO, our shared lead investigational gene therapy, will soon reach patients in its first clinical trial, offering new promise to children with this rare form of congenital hearing loss, as well as potential proof-of-concept for future gene therapies addressing more common forms of genetic hearing loss. We believe that Decibel’s assets and specialized team will further strengthen our genetic medicines portfolio, enabling Regeneron to accelerate the development of innovative genetic therapies and a rich pipeline of hearing loss treatments."

Congenital hearing loss is a significant unmet medical need with no approved medical therapies that affects approximately 1.7 out of every 1,000 children born in the United States. While hearing loss caused by mutations of the otoferlin gene is rare, the majority of permanent, congenital hearing loss cases diagnosed in developed countries are sensorineural and result from a single gene defect, making them appealing targets for gene therapy. Hearing aids and cochlear implants may offer benefits, but they fall short of replicating normal hearing function.

The merger agreement provides for Regeneron, through its wholly owned subsidiary Symphony Acquisition Sub, Inc., to initiate a tender offer to acquire all outstanding shares of Decibel at a price of $4.00 per share of Decibel common stock payable in cash at closing plus one CVR payable in cash subject to the terms and conditions contained in a contingent value rights agreement ("CVR Agreement"). CVR holders would become entitled to receive contingent payments as follows: (i) $2.00 in cash, upon the fifth participant being administered with DB-OTO in a clinical trial on or prior to December 31, 2024 (the DB-OTO Milestone); and (ii) $1.50 in cash, upon (a) the first participant being administered with DB-OTO in a registration enabling trial (as defined in the CVR Agreement) or (b) acceptance for review of a Biologics License Application by the U.S. Food and Drug Administration, a Marketing Authorization Application by the European Medicines Agency or the U.K. Medicines and Healthcare Products Regulatory Agency, or an equivalent application by the applicable national regulatory authority in any of Germany, France, Italy or Spain for DB-OTO, whichever occurs first, on or prior to December 31, 2028; provided the DB-OTO Milestone is achieved on or prior to December 31, 2024. There can be no assurance that any payments will be made with respect to the CVR. The closing of the tender offer will be subject to certain conditions, including the tender of at least a majority of the outstanding shares of Decibel common stock and other customary closing conditions. Upon the successful completion of the tender offer, Regeneron will acquire all shares not acquired in the tender through a second-step merger for the same consideration per share paid in the tender offer. The transaction is expected to close in the third quarter of 2023.

Regeneron’s legal advisor for the transaction is Wachtell, Lipton, Rosen & Katz. Centerview Partners LLC and Leerink Partners LLC are serving as Decibel’s financial advisors and Wilmer Cutler Pickering Hale and Dorr LLP is serving as Decibel’s legal advisor.

On August 9, 2023 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical leader in cell cycle checkpoint control developing innovative medicines based on cancer cell biology, reported second quarter financial results and provided a business update (Press release, Cyclacel, AUG 9, 2023, View Source [SID1234634059]).

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"Both clinical programs with fadraciclib and plogosertib are progressing well, and we are on track to report on important readouts this year," said Spiro Rombotis, President and Chief Executive Officer. "Based on data collected to date we believe that fadraciclib’s next generation CDK inhibitor profile is differentiated from other molecules in its class. Similarly plogosertib could emerge as a PLK1 inhibitor with novel epigenetic activity. We look forward to presenting data from these two programs in the coming months."

"We are completing dose escalation level 6A with six patients in the 065-101 study of fadraciclib as a single agent and expect to select the recommended Phase 2 dosing schedule shortly. A patient with endometrial cancer in dose level 6A has documented tumor shrinkage after one cycle," said Mark Kirschbaum, M.D., Chief Medical Officer. "In the 140-101 study of plogosertib as a single agent we are recruiting patients at dose level 5. Anticancer activity has been observed thus far in four out of twelve patients, with adenoid cystic carcinoma, biliary, non-small cell lung, and ovarian cancer respectively, who stayed on treatment for three to eight cycles. The activity at low level, continuous exposure may be due to the effects of plogosertib operating through a novel epigenetic mechanism which we are continuing to investigate. If confirmed, we will design clinical studies that could exploit these findings."

Key Upcoming Milestones

• Report final data from dose escalation stage and RP2D determination from the 065-101 study of oral fadraciclib in patients with advanced solid tumors and lymphoma
• First patient dosed with oral fadraciclib in Phase 2 proof-of-concept stage of 065-101 study in patients with advanced solid tumors and lymphoma
• Report Phase 1 data from 140-101 study of oral plogosertib in patients with advanced solid tumors and lymphoma
• Elaborate novel mechanism of action of plogosertib

Financial Highlights

As of June 30, 2023, cash equivalents totaled $10.2 million, compared to $18.3 million as of December 31, 2022. Net cash used in operating activities was $8.2 million for the six months ended June 30, 2023 compared to $8.7 million for the same period of 2022. The Company estimates that its available cash will fund currently planned programs through the end of 2023. The operating plan includes discretionary expenditures, which if not incurred could extend liquidity requirements into the second quarter of 2024.

Research and development (R&D) expenses were $4.7 million for the three months ended June 30, 2023, as compared to $4.2 million for the same period in 2022. R&D expenses relating to fadraciclib were $3.0 million for the three months ended June 30, 2023, as compared to $2.6 million for the same period in 2022 due to increased non-clinical expenditures. R&D expenses related to plogosertib were $1.4 million for the three months ended June 30, 2023, as compared to $1.5 million for the same period in 2022 due to clinical trial costs associated with the progression of the Phase 1/2 study.

General and administrative expenses for the three months ended June 30, 2023 and 2022, remained relatively flat at $1.6 million.

Total other expense, net, for the three months ended June 30, 2023, was $0.1 million compared to an income of $0.2 million for the same period of the previous year.

United Kingdom research & development tax credits for the three months ended June 30, 2023 were $0.6 million compared to $1.0 million for the same period of the previous year due to taxation legislative changes that took effect in April 2023. Research & development tax credits are directly correlated to qualifying research and development expenditure.

Net loss for the three months ended June 30, 2023, was $5.4 million, compared to $4.6 million for the same period in 2022.

Conference call information:

Call: (800) 225-9448 / international call: (203) 518-9708

Archive: (800) 839-6136 / international archive: (402) 220-2572

Code for live and archived conference call is CYCCQ223. Webcast link

For the live and archived webcast, please visit the Corporate Presentations page on the Cyclacel website at www.cyclacel.com. The webcast will be archived for 90 days and the audio replay for 7 days.

On August 9, 2023 Clarity Pharmaceuticals (ASX: CU6) ("Clarity", "the Company"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported the successful completion of cohort 2 and advancement to cohort 3 in the dose escalation phase of its Phase I/II theranostic trial, SECuRE, evaluating 64Cu/67Cu SAR-bisPSMA in patients with mCRPC (Press release, Clarity Pharmaceuticals, AUG 9, 2023, View Source [SID1234634058]).

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The SECuRE trial (NCT04868604)1 is a Phase I/IIa theranostic trial for identification and treatment of Prostate-Specific Membrane Antigen (PSMA) expressing mCRPC using 64Cu/67Cu SAR-bisPSMA. 64Cu SAR-bisPSMA is used to visualise PSMA expressing lesions and select candidates for subsequent 67Cu SAR-bisPSMA therapy. The trial is a multi-centre, single arm, dose escalation trial with a cohort expansion involving up to 44 patients in the US. The aim of the trial is to determine the safety and efficacy of 67Cu SAR-bisPSMA for the treatment of prostate cancer.

The second cohort of the dose escalation, where 3 participants received a single administration of 8GBq of 67Cu SAR-bisPSMA, has been completed. No DLTs have been reported in any of the patients dosed to date. The SRC, responsible for assessing safety of participants and overseeing the general progress of the trial, has assessed the data and recommended progressing the trial to cohort 3, increasing the dose to 12GBq. The third cohort will be the last to assess single doses of 67Cu SAR-bisPSMA and will be followed by a multi-dose cohort, pending safety evaluation. The 3 participants in cohort 2 have been monitored by their physicians for safety and treatment response as per the trial protocol. All 3 participants in cohort 2 remain on the trial following their recent administration of 8GBq of 67Cu SAR-bisPSMA and are demonstrating a PSA reduction, with 2 of the 3 participants exhibiting an initial PSA reduction of ~90%. A PSA decline of 50% or greater is one of the primary endpoints of the SECuRE trial and a commonly used surrogate endpoint for efficacy in this patient population.

Dr Luke Nordquist, CEO, Urologic Medical Oncologist and Principal Investigator at the Urology Cancer Center / XCancer Omaha, NE, commented, "We are excited by the remarkable PSA declines seen in all three patients in cohort 2 with just a single dose of 8GBq of 67Cu SAR-bisPSMA. I have not observed PSA responses like this after a single dose of any agent and, considering the excellent safety profile we have seen to date in the first two cohorts of this study, we really look forward to progressing the development of this promising therapy. While in the VISION trial2 with 177Lu PSMA-617 we did see a >80% reduction in PSA in roughly 33% of patients, this was after up to six 7.4GBq doses of 177Lu PSMA-617 spaced out over a period of up to 30 weeks. If a single 8GBq dose of 67Cu SAR-bisPSMA can deliver so much benefit to the patients, we are excited to see how a single 12GBq dose will benefit patients in cohort 3 and to explore the effect of multiple dosing. If similar responses can be replicated in larger patient numbers, 67Cu SAR-bisPSMA may become the gold standard therapeutic agent for patients with mCRPC once approved."

Additional therapy cycles of 67Cu SAR-bisPSMA have been requested by clinicians under the FDA EAP for patients who participated in the SECuRE trial. SPECT-CT images depicted below were collected 48 hours after the first, third and fourth administrations of 4GBq of 67Cu SAR-bisPSMA in a patient from cohort 1 who received additional cycles under the EAP.

SPECT-CT images collected following the third and fourth therapy cycle demonstrate a reduction in the intensity of therapeutic 67Cu SAR-bisPSMA product uptake at the tumour sites. A reduction of greater than 50% in PSA levels was observed in this patient following the first administration of 4GBq of therapeutic 67Cu-SAR-bisPSMA and a drop of greater than 90% in PSA was observed after the fourth administration of 4GBq of 67Cu-SAR-bisPSMA.

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "We are very excited to observe such a dramatic response in prostate cancer patients from cohort 2 following a single dose of 8GBq of 67Cu SAR-bisPSMA. SAR-bisPSMA aims to be a best-in-class PSMA product due to its differentiation from all other PSMA-targeted products in the market and in development that only have a single PSMA-targeting agent. We purposely designed and optimised SAR-bisPSMA to have two PSMA-targeting agents to address the challenges of low uptake and retention that the first generation of PSMA products suffer from. In pre-clinical and clinical development to date, we have observed two to three times the uptake of SAR-bisPSMA in tumours, followed by retention in tumours out to at least 96 hours. Although our data is early, the higher uptake and retention of product, coupled with the advantageous properties of copper-67, has shown quite impressive responses from single doses and we look forward to exploring the clinical benefits of 67Cu SAR-bisPSMA at the higher 12GBq level and over multiple treatment cycles. With commercial quantities of the 67Cu radioisotope now being routinely produced domestically in the US by our exclusive supplier, NorthStar, we see a clear path to commercialisation as we continue to push forward through clinical trials for 67Cu SAR-bisPSMA and bringing this product to the greater prostate cancer patient population.

"Prostate cancer is one of the largest oncology indications worldwide and, based on our estimates, represents a US$5-10 billion therapy market for PSMA targeting radiopharmaceuticals. Radiopharmaceuticals are expected to play an increasingly important role in the management of patients with prostate cancer, however, challenges associated with the current generation of products prevail. Clarity’s Targeted Copper Theranostic (TCT) platform represents the next-generation platform in radiopharmaceuticals to improve treatment outcomes for children and adults with cancer as well as resolve the supply and manufacturing issues associated with the first generation of products. Because of these characteristics, TCTs are ideally positioned to enable the field to expand into the oncology market, addressing large indications such as prostate cancer and beyond.

"We look forward to sharing more data on 67Cu SAR-bisPSMA as the SECuRE trial continues to progress and any further updates from patients who may receive single or multiple doses of 67Cu SAR-bisPSMA in our programs," said Dr Taylor.

About SAR-bisPSMA
SAR-bisPSMA derives its name from the word "bis", which reflects a novel approach of connecting two PSMA-targeting agents to Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-bisPSMA is a TCT that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.