On June 14, 2022 Blue Earth Therapeutics, a Bracco company and emerging leader in the development of innovative next generation therapeutic radiopharmaceuticals, reported results from a series of preclinical analyses designed to evaluate the biodistribution and potential therapeutic efficacy of 177Lu-rhPSMA-10.1 and 177Lu-PSMA-I&T in the treatment of prostate cancer preclinical models (Press release, Blue Earth Therapeutics, JUN 14, 2022, View Source [SID1234615976]). Results from preclinical biodistribution studies demonstrated that 177Lu‑rhPSMA-10.1 performed favorably when compared with 177Lu-PSMA-I&T, with an improved tumor:kidney uptake ratio. Therapeutic efficacy was evaluated in a preclinical prostate cancer xenograft model which showed that 177Lu‑rhPSMA‑10.1 significantly suppressed tumor growth relative to control, and to a greater extent than 177Lu-PSMA-I&T. The data were presented in an oral presentation at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting. 177Lu-rhPSMA-10.1 is an investigational radiohybrid (rh) Prostate-Specific Membrane Antigen-targeted therapeutic radiopharmaceutical, and the lead candidate in Blue Earth Therapeutics’ oncology development program of next generation therapeutic radiopharmaceuticals.

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"Radioligand therapy targeting prostate-specific membrane antigen (PSMA) has been shown to be an effective therapy in men with metastatic castration-resistant prostate cancer," said Caroline Foxton, Ph.D., Vice President R&D Strategy and Collaboration at the Blue Earth Group. "However, optimizing tumor uptake and accelerating renal clearance for this class of compounds could improve the therapeutic index, achieve better clinical outcomes and effectively manage radiation exposure to patients. Blue Earth Therapeutics’ next generation therapeutic rhPSMA compound has been optimized for favorable biodistribution properties to enhance delivery of therapeutic radiation to tumors while minimizing kidney uptake and retention. Supported by these preclinical data, 177Lu‑rhPSMA-10.1 was selected as our lead therapeutic candidate for progression to the clinic."

"We are pleased that the first presentation of preclinical results from Blue Earth Therapeutics’ rhPSMA-10.1 program in prostate cancer is being made to the nuclear medicine community at the SNMMI 2022 Annual Meeting," said David E. Gauden, D.Phil., Chief Executive Officer of the Company. "Radiohybrid PSMA technology enables utility as a theranostic because the molecule may be modified and deployed for either diagnostic PET imaging or therapeutic applications. This optimized rhPSMA technology can also be developed with both beta- and alpha-emitting therapeutic radioisotopes, with the potential to deliver personalized, targeted therapy specific to each patient’s condition. We are closely collaborating in the development of 177Lu-rhPSMA-10.1 with our sister company, Blue Earth Diagnostics, by incorporating its investigational 18F-rhPSMA-7.3 PET agent into our clinical development program."

Dr. Gauden continued, "Results from these analyses demonstrate the attractive preclinical biodistribution and potential therapeutic efficacy profile of 177Lu-rhPSMA-10.1, and were included in our Investigational New Drug application to the U.S. Food and Drug Administration. Blue Earth Therapeutics’ Phase 1/2 clinical trial for 177Lu-rhPSMA-10.1 in treating men with metastatic castrate‑resistant prostate cancer was recently cleared to proceed, and we expect patient enrollment to commence shortly."

Results
The findings presented at SNMMI included biodistribution data from preclinical models which evaluated 177Lu-rhPSMA-10.1 and 177Lu-PSMA-I&T uptake and tumor:kidney ratio, and therapeutic efficacy analysis in preclinical prostate cancer xenograft models.

Biodistribution
Data from longitudinal biodistribution analyses in preclinical models showed that the most significant organ uptake for both 177Lu-rhPSMA-10.1 and 177Lu-PSMA-I&T was observed in the kidney; however, kidney retention was lower for 177Lu-rhPSMA-10.1 than 177Lu-PSMA-I&T at all timepoints, and 6.5-fold lower than that for 177Lu-PSMA-I&T at 12 hours. No other organ (including the brain) showed any significant uptake of 177Lu-rhPSMA-10.1. A single-timepoint biodistribution study using a PSMA-expressing prostate cancer xenograft model examined the tumor:kidney uptake ratio for both compounds. It also showed lower kidney uptake of 177Lu‑rhPSMA‑10.1, with kidney uptake being 6.4‑fold lower for 177Lu-rhPSMA-10.1 than for 177Lu‑PSMA-I&T at 15 hours post-injection. Higher tumor uptake was seen with 177Lu‑rhPSMA‑10.1 than 177Lu-PSMA-I&T at this timepoint (2.3-fold), resulting in an improved tumor:kidney ratio for 177Lu-rhPSMA-10.1 (2.3±1.14) compared to 177Lu-PSMA-I&T (0.1±0.03).

Efficacy
The potential therapeutic efficacy of 177Lu-rhPSMA-10.1 and 177Lu-PSMA-I&T was compared in a PSMA-expressing prostate cancer xenograft model. Tumor volume was significantly reduced by 177Lu-rhPSMA-10.1 compared with the vehicle control (p=0.045 at 35 days after treatment). When measuring fold-change in tumor volume relative to volume at inclusion, 177Lu-rhPSMA-10.1 showed a statistically significant suppression of tumor growth compared to both non-radiolabeled rhPSMA-10.1 and vehicle control at both 14 days after treatment (p<0.01 both comparisons) and 35 days after treatment (p<0.01 vs non-radiolabeled rhPSMA-10.1 and p<0.001 vs vehicle). 177Lu-PSMA-I&T also reduced tumor growth compared with vehicle control (p<0.05), but to a lesser extent than 177Lu‑rhPSMA‑10.1. No significant effects were noted on any hematological parameters or body weight.

The results were discussed in an oral presentation, "Preclinical evaluation of a novel radioligand therapy for patients with prostate cancer: biodistribution and efficacy of 177Lu-rhPSMA-10.1 in comparison with 177Lu-PSMA-I&T," by Caroline Foxton, Ph.D., Blue Earth Group, Oxford, UK, at the SNMMI 2022 Annual Meeting on June 13, 2022. Full session details and the abstract are available in the SNMMI online program HERE.

About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)
rhPSMA compounds are referred to as radiohybrid ("rh"), as each molecule possesses three distinct domains. The first consists of a Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells. It is attached to two labelling moieties which may be radiolabeled with either 18F for PET imaging, or with isotopes such as 177Lu or 225Ac for therapeutic use – creating a true theranostic technology. They may play an important role in patient management in the future, and offer the potential for precision medicine for men with prostate cancer. 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 has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Therapeutics and Blue Earth Diagnostics work closely on the development of 177Lu-rhPSMA-10.1. Currently, rhPSMA compounds have not received regulatory approval.

On June 14, 2022 AVM Biotechnology, a clinical stage company advancing AVM0703 in the treatment of Non-Hodgkin’s Lymphoma (NHL)/Leukemia, reported that it has been awarded a Phase II Small Business Innovative Research (SBIR) grant (Press release, AVM Biotechnology, JUN 14, 2022, View Source [SID1234615975]). This $2 million National Cancer Institute (NCI) grant will assist in the continuation of the company’s existing clinical trial (AVM0703 for Treatment of Leukemia or Lymphoma, NCT04329728).

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This Phase II grant has been awarded for continued support of the adaptive-design, expansion cohort clinical trial of AVM0703 for "no-option," Relapsed/Refractory (R/R) NHL/Leukemia patients. The study is currently enrolling at City of Hope, UCLA, Norton Cancer Institute, and the University of Texas Southwestern. Additional sites are being brought on-line.

AVM0703:

is a small molecule which triggers the production and release of endogenous bispecific gamma delta TCR+ invariant TCR+ Natural Killer T-like cells (AVM-NKT).
induces AVM-NKT cells rapidly in the blood following a single dose.
is currently the subject of an adaptive design expansion cohort clinical trial with the dose escalation phase nearing completion and the efficacy phase projected to commence soon.
In the ongoing dose escalation phase, which included 11 highly refractory patients who had been heavily pretreated averaging 5.3 prior lines of therapy with 6 of 11 having failed hematopoietic stem cell transplantation (HSCT) or CAR-T, results included:

100% clinical response at 18 mg/kg target Ph II dose, with durable partial response/stable disease ongoing out to greater than 9 months in 1 patient.
Of 10 evaluable patients from the dose-escalation; 4 experienced partial response and 2 other patients subsequently reached complete remission.
An additional 20% achieved stable disease or significant clinical response including durable vision restoration in 1 patient.
One heavily pretreated patient with T-cell lymphoma who did not meet inclusion/exclusion criteria received AVM0703 under an FDA-approved Compassionate Use Program. That patient has experienced a very good partial response.

The drug has been well-tolerated with no reported Dose Limiting Toxicities (DLTs) or grades 4 or 5 adverse events. AVM0703 also potentiates chemotherapy and CAR-T response in pre-clinical models.

NHL is the 7th most common cancer in the US with over half of the 77,240 diagnosed annually over the age of 65. Even with treatment, disease recurs or relapses in approximately 50% of these patients and many become refractory to additional treatment. Patients can undergo many lines of various therapies including chemotherapy, radiation, CAR-T and HSCT which can be associated with significant toxicities and poor outcomes with many relapsing and requiring additional treatment. Based on its strong safety profile and clinical response, AVM0703 presents an appealing alternative to these therapies.

"AVM0703 represents an exciting new treatment option for NHL patients who have failed other therapies or who do not qualify for further chemotherapy, radiation, or cell therapies, including CAR-T. In addition to improvement in disease status, several patients treated with AVM0703 in the dose-escalation phase of the study have qualified for other treatments they had formerly been excluded from accessing," said Joe Luminiello, CEO.

AVM Biotechnology previously received a Phase I NCI grant from the National Institutes of Health (NIH) to study the use of AVM0703 as a preconditioning agent to allow safe and efficient delivery of therapeutic immune cells for cancer treatment. The company has requested breakthrough therapy designation and plans for accelerated approval for commercial launch in mid 2024.

On June 14, 2022 CDx Diagnostics, Inc. reported that it has signed an agreement with laboratory benefits management provider Avalon Healthcare Solutions, Inc. of Tampa, Fla (Press release, CDx Diagnostics, JUN 14, 2022, View Source [SID1234615974]). The agreement means that CDx will be an in-network specialty anatomic pathology laboratory of Avalon client BlueCross BlueShield of South Carolina, and builds on Avalon’s positive medical policy for CDx’s proprietary diagnostic platform, WATS3D.

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Short for wide-area transepithelial sampling with three-dimensional analysis, WATS3D utilizes enhanced tissue acquisition, 3D imaging with AI-powered analysis, and expert pathologists to reliably detect Barrett’s esophagus (BE) and esophageal dysplasia. Effectively immediately, the agreement makes WATS3D available to the 565,000 members of BCBS of South Carolina with all commercial and Medicare Advantage plans.

"At CDx, we’re driven to empower physicians to preempt esophageal cancer and improve patient lives," said Bill Huffnagle, CEO of CDx Diagnostics. "This new agreement with Avalon brings modern, proven diagnostic technology to more than half a million more members. We will work together to bring this potentially lifesaving technology to additional payors and the members they serve."

WATS3D technology helps clinicians overcome the limitations associated with traditional upper endoscopy screening and surveillance methods, by combining a specially designed brush, unique 3D imaging powered by AI, and a team of trained GI pathologists. In large multicenter clinical studies, WATS3D has been found to significantly increase the detection rate of BE and esophageal dysplasia, both treatable precursors to esophageal cancer, one of the fastest growing and most fatal cancers in the United States.

On June 14, 2022 Spirea Limited, a Cambridge company created to advance a new generation of antibody drug conjugate (ADC) therapeutics, reported that it has secured funding of £2.4 million with investments from high-profile UK and US investors (Press release, Spirea, JUN 14, 2022, View Source [SID1234615973]). Spirea will use the funds to initiate its pipeline of superior and differentiated ADCs in the treatment of solid tumours where there is a high unmet need.

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ADCs combine the cell killing activity of a cytotoxic drug with the cancer targeting capability of a monoclonal antibody. Although the ADC concept has been exemplified with approved products, many ADC programmes have failed to progress through clinical development because of dose-limiting toxicities, restricted efficacy, and limitations in the range of treatable cancers.

Spirea’s technology allows more cytotoxic drug to be attached to the targeting antibody (a higher drug-to-antibody ratio) which means more drug is delivered to the cancer cell. This allows for the development of stable and tailored ADCs incorporating a variety of drug payloads at varying levels of potency and different modes-of-action. This will result in cancer therapeutics with significantly better efficacy and safety profiles.

Dr Myriam Ouberai, Chief Executive Officer at Spirea, commented: "We welcome our new investors and thank our existing investors for their continuing confidence in Spirea. With our novel approach to building ADC therapeutics, we aim to radically improve the treatment options for patients with hard-to-treat cancers. Having shown the flexibility and strength of our technology, we look forward to the next exciting stage in the development of Spirea’s ADC pipeline and to building significant strategic partnerships."

Dr Christine Martin, Head of Seed Funds at Cambridge Enterprise, said: "This is an exciting time for Spirea and we are pleased to be supporting them with this further investment. Spirea’s innovative antibody drug conjugate technology is highly differentiated, and we believe it holds great value and potential to lead developments in the field of cancer therapeutics."

Dr Jonathan Milner, Founder of Abcam and CEO of Meltwind Advisory, said: "Spirea has overcome many of the hurdles commonly associated with antibody drug conjugate therapeutics. By developing a highly customisable platform where drug payloads and targets can be altered as needed, the Company is revealing the true potential of ADCs as a cancer cell specific, highly effective therapeutic option for a wide range of cancers."

Spirea, a spin-out from the University of Cambridge, has previously received investment from IP Group, Cambridge Enterprise, Start Codon, Jonathan Milner, o2h Ventures and Syndicate Room, and is supported by a number of successful, high-profile board members from the life sciences.

On June 14, 2022 Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY, NSEIFSC: DRREDDY, along with its subsidiaries together referred to as "Dr. Reddy’s") reported the launch of Dr. Reddy’s Sorafenib Tablets, USP, 200 mg, a therapeutic generic equivalent of Nexavar (sorafenib) Tablets in the U.S. market following the approval by the U.S. Food and Drug Administration (USFDA) (Press release, Dr Reddy’s, JUN 14, 2022, View Source [SID1234615972]).

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"We are pleased to launch this important generic product, illustrating our continued commitment to bring affordable generic medicines to market for patients," says Marc Kikuchi, Chief Executive Officer, North America Generics, Dr. Reddy’s Laboratories Inc.

Dr. Reddy’s Sorafenib Tablets, USP, are available in 200 mg tablets in bottle count sizes of 120.

Please click here: View Source to see the full prescribing information.

Nexavar is a trademark of Bayer HealthCare Pharmaceuticals Inc.

RDY-0522-415