On December 17, 2021 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported that it has reached its target enrollment of 12,750 patients in ECLIPSE (Evaluation of ctDNA LUNAR Assay In an Average Patient Screening Encounter), a registrational study to evaluate the performance of its LUNAR-2 blood test to detect colorectal cancer (CRC) in average-risk adults (Press release, Guardant Health, DEC 17, 2021, View Source [SID1234597434]). Subject to positive study results, the number of patients currently enrolled in ECLIPSE is targeted to support a premarket approval (PMA) submission to the U.S. Food and Drug Administration in 2022.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Colorectal cancer screening rates have remained stubbornly low due to the nature of current screening methods. New modalities in colorectal cancer screening, such as a routine, accurate blood test like the one being studied in the ECLIPSE study, has the potential to increase screening rates dramatically," said AmirAli Talasaz, Guardant Health co-CEO. "Reaching this significant enrollment milestone highlights our ability to successfully run one of the largest cancer screening studies of its kind and gives us tremendous confidence in initiating large registrational studies in other cancer types, including the SHIELD screening study to detect lung cancer. It is also a testament not just to our team’s perseverance, but also to the commitment of our clinical researchers and the generosity of those enrolled in the study."

Today, it is estimated that 1 in 3 adults in the U.S. does not adhere to national CRC screening recommendations even though regular screening for colorectal cancer has been shown to improve survival rates.1,2 Increasing screening rates to 80% from current levels could reduce the number of people diagnosed with CRC by 22% by 2030.3 However, current screening methods are time consuming and, in the case of a colonoscopy, invasive. LUNAR-2 is intended to improve CRC screening rates by offering a simple blood test that overcomes barriers associated with current testing methods and facilitates access to screening tests to more individuals and communities where access may be limited.

"Given the importance of this study and the size of the cohort, we’re grateful Guardant Health has been able to enroll 12,750 study participants in just over two years during a global pandemic," said William M. Grady, M.D., Professor, Clinical Research Division, Fred Hutchinson Cancer Research Center. "We look forward to evaluating the data from the ECLIPSE study to increase our understanding of blood-based screening in patients at average risk for colorectal cancer."

ECLIPSE is a prospective, multi-site registrational study to evaluate the performance of the company’s LUNAR-2 blood test to detect colorectal cancer in individuals aged 45-84 in the U.S. who are at average risk for colorectal cancer, including those who have historically been underrepresented in clinical research and identify as Native American and Black or African American. More details about ECLIPSE can be found at NCT04136002.

On December 17, 2021 Chimeric Therapeutics (ASX:CHM, "Chimeric"), a clinical-stage cell therapy company and the ASX leader in cell therapy, reported the successful completion of the 2nd dose cohort in the CLTX CAR T phase 1 dose escalation study at the City of Hope, a world-renowned cancer research and treatment organization near Los Angeles (Press release, Chimeric Therapeutics, DEC 17, 2021, View Source [SID1234597356]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

All patients in the 2nd dose cohort were dosed with a total dose of 88 X 106 CLTX CAR T cells (double that used in the first dose cohort) and have now advanced past the 28 day follow up period without experiencing any dose limiting toxicities.

The successful completion of this 2nd patient cohort is a significant milestone for CLTX CAR T cell therapy as the 2nd dose cohort introduced dual routes (intraventricular and intratumoral) of CLTX CAR T administration.

The study now advances to the 3rd dose cohort, which will administer CLTX CAR T cells to patients through the dual routes of administration at an increased total dose of 220 X 106 CLTX CAR T cells.

"Chimeric is incredibly pleased to have reached this important milestone with our CLTX CAR T cell therapy. Demonstrating safety with dual routes of administration (ICT and ICV) at this 2nd CLTX CAR T dose level is very encouraging. We now look forward to further advancing the development of CLTX CAR T as we enter the 3rd dose level in the trial," said Jennifer Chow, Chimeric Therapeutics Chief Executive Officer.

About the CLTX CAR T (CHM1101) Clinical Trial:
The CLTX CAR T phase 1 clinical trial is currently in progress at a single site in California with plans to expand to a multi-site trial in 2022. The design is a single arm trial in patients with MMP2+ recurrent or progressive glioblastoma.

The primary endpoints of the trial are to assess the safety of CLTX CAR T cells, determine the maximum tolerated dose schedule and a recommended Phase 2 dosing plan. Secondary endpoints include bioactivity and efficacy measures.

The trial is designed with 4 dose levels ranging from 44 X 106 to 440 X 106 CLTX CAR T cells and studies both single and dual routes of administration of cells. Dose level 1 was completed with no dose limiting toxicities in April 2021. Authorised on behalf of the Chimeric Therapeutics board of directors by Chairman Paul Hopper.

ABOUT CHLOROTOXIN CAR T
Chlorotoxin CAR T (CLTX CAR T) cell therapy is a first and best in class CAR T cell therapy that has the potential to address the high unmet medical need of patients with recurrent/ progressive glioblastoma. Research to develop the intellectual property covering this CAR T cell therapy took place at City of Hope.

CLTX CAR T cell therapy uniquely utilizes chlorotoxin (CLTX), a peptide derived from scorpion toxin, as the tumour-targeting component of the chimeric antigen receptor (CAR). CLTX and CLTX CAR T cells have been shown in preclinical models to bind more broadly and specifically to GBM cells than other targeting domains like EGFR, HER-2 or IL-13.

In preclinical models, CLTX CAR T cells also demonstrated potent antitumor activity against glioblastoma while not exhibiting any off-tumor recognition of normal human cells and tissues, indicating a potentially optimal safety and efficacy profile

On December 17, 2021 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) ("Sonnet" or the "Company"), a biopharmaceutical company developing innovative targeted biologic drugs, reported its financial results for the fiscal year ended September 30th, 2021 and provided a business update (Press release, Sonnet BioTherapeutics, DEC 17, 2021, View Source [SID1234597375]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Pankaj Mohan, Ph.D., Founder and CEO commented, "This year has been incredibly exciting for Sonnet. We identified a new bispecific candidate, SON-1410, and were granted patent-protection for our FHAB technology. Additionally, we generated compelling new data to progress our therapeutic pipeline, including successful preclinical studies for SON-1010 and SON-080, which set the stage for future clinical studies. We believe this positions us well for continued growth and advancement of our pipeline in 2022."

Fiscal Year 2021 and Recent Corporate Updates

Financings Completed: On August 24th, Sonnet successfully completed its follow-on offering of 35,294,117 shares of common stock and investor warrants for total net proceeds of approximately $27.6 million.

In June 2021, Sonnet completed the final issuance of shares of its common stock under the At-the-Market Sales Agreement, pursuant to which the Company executed issuances of an aggregate of 7,454,238 shares for total net proceeds of $15.2 million.

Issuance of U.S. Patent for Platform Technology: On June 8th, Sonnet announced the USTPO issued U.S. Patent No. 11,028,166 entitled, "Albumin Domain Fusion Proteins". The patent covers Sonnet’s Fully Human Albumin Binding (FHAB) technology and includes therapeutic fusion proteins that utilize FHAB for tumor targeting and retention and provide extended pharmacokinetics (PK). The patent carries a term effective until March 2039.

Completed Licensing Agreement with New Life Therapeutics: On May 3rd, Sonnet announced a definitive agreement with New Life Therapeutics of Singapore for the license of low-dose Interleukin 6, or IL-6, for the treatment of Diabetic Peripheral Neuropathy (DPN). The licensed territory includes the ASEAN countries of Singapore, Malaysia, Indonesia, Thailand, The Philippines, Cambodia, Brunei, Vietnam, Myanmar and Lao PDR.

Appointment of Richard Kenney and Manuel DaFonseca: On March 22nd, Sonnet announced the appointment of Richard Kenney, M.D. as Chief Medical Officer and Manuel DaFonseca, as Head of Clinical Operations.

Sonnet is pleased to provide the following updates on its pipeline assets:

SON-1010 (IL12-FHAB): On February 1st, Sonnet announced that it had successfully completed a non-human primate (NHP), non-GLP repeat-dose toxicology study of SON-1010. The drug candidate was well tolerated at doses far exceeding levels expected in future human clinical trials, without producing detectable cytokine imbalances. SON-1010 demonstrated an enhanced pharmacokinetic (PK) profile as compared to recombinant IL-12. Analysis of interferon-γ levels, a key biomarker of antitumor activity, continued to suggest potent pharmacodynamic (PD) effects in the monkeys studied.

On May 10th, Sonnet announced the completion of a successful GLP repeat dose toxicology study of SON-1010 in NHPs. The No Observed Adverse Event Level (NOAEL) following repeated administration was more than 50 times the anticipated equivalent human clinical dose in NHPs with no evidence of cytokine release syndrome. PK analysis of serum samples confirmed an enhanced profile of IL12-FHAB over recombinant human IL-12, with a half-life around 40 hours in NHPs. A significant increase in interferon-γ, a key pleiotropic cytokine associated with anti-tumor mechanisms, was observed following dosing with IL12-FHAB.

An IND for SON-1010 has been submitted to the FDA and additional product stability data will be submitted in the first quarter of 2022. Subject to FDA approval, we expect to initiate a US clinical trial in oncology patients with solid tumors during the first half of 2022. We are also preparing to initiate an Australian clinical trial in healthy volunteers during the first half of 2022 to study the compound’s PK and PD, in preparation for potential combination studies.

SON-080 (low-dose IL-6): On January 25th, Sonnet announced that Sonnet CH, a wholly owned subsidiary of Sonnet headquartered in Switzerland, had successfully completed a multiple dose NHP study of SON-080. The toxicology study demonstrated a wide safety margin with no adverse effects observed in male or female cynomolgus monkeys at the doses tested. Sonnet intends to file for an ex-US Phase 1b/2a pilot-scale efficacy study with SON-080 in CIPN during the first half of 2022. Pursuant to the license agreement the Company entered with New Life Therapeutics Pte., Ltd of Singapore in May 2021, Sonnet and New Life will be jointly responsible for developing SON-080 in DPN with the objective of initiating an ex-US pilot efficacy study in the second half of 2022.

SON-1210 (IL12-FHAB-IL15): SON-1210, Sonnet’s first bispecific candidate, is undergoing cell line and process development activities. Early development materials were used in a mouse tumor model study, and additional biodistribution studies are planned. This work will inform the Company’s decision about dosing in a forthcoming NHP study, expected to be initiated in the first half of 2022. Scale up and cGMP manufacturing is scheduled to be completed in the first half of 2022, which will support the GLP NHP study, as well as First-In-Human (FIH) studies. Sonnet expects to initiate the regulatory authorization process for solid tumor indications in the second half of 2022.

SON-1410 (IL18-FHAB-IL12): On August 30th, Sonnet announced that it had selected a novel development candidate after completing comparative studies in a mouse melanoma model. The candidate represents Sonnet’s second bispecific compound integrating interleukin 12 (IL-12) with the company’s FHAB platform. The target indications for SON-1410 will be melanoma and renal cancers.

Fiscal Year Ended September 30, 2021 Financial Results

Jay Cross, CFO, elaborated on Sonnet’s 2021 fiscal year results, saying, "The Company has made important forward progress with our balance sheet this fiscal year, and we expect to continue to deliver on our stated objectives of advancing our therapeutic pipeline. We believe we are in a good position to maintain our positive momentum through 2022."

●As of September 30, 2021, Sonnet had $27.6 million cash on hand, an increase from last quarter after a public offering in which the Company sold 33,193,485 shares of its common stock and pre-funded warrants to purchase 2,100,632 shares of common stock.
●The Company currently has outstanding 60,250,637 shares of common stock and warrants to purchase an aggregate of 51,789,522 shares of common stock, with a weighted average exercise price per share of $1.45. In the event all warrants were exercised for cash, the Company could receive up to $75.2 million of additional capital.

Research and development expenses were $16.6 million for the year ended September 30, 2021, compared to $9.9 million for the year ended September 30, 2020. The increase of $6.8 million was primarily due to the development of the cell lines for IL12-FHAB, IL12-FHAB-IL15 and SON-080, and an increase in payroll and share-based compensation expense, as we continue to expand our operations. General and administrative expenses were $8.9 million for the year ended September 30, 2021, compared to $7.5 million for the year ended September 30, 2020. The increase of $1.4 million was primarily due to an increase in payroll and share-based compensation expense and insurance expenses related to directors and officer’s insurance, as we continue to expand our operations to support our research and development efforts, partially offset by a $1.4 million decrease in professional fees and transaction related fees.

On December 17, 2021 DisperSol Technologies LLC reported that it is has entered into a research collaboration with Ajax Therapeutics, Inc. to apply its KinetiSol technology to enhance the bioavailability of an Ajax drug candidate in development for the treatment of hematologic malignancies (Press release, Ajax Therapeutics, DEC 17, 2021, View Source [SID1234597435]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Ajax is taking an innovative approach to developing a pipeline of selectively targeted small molecules and we look forward to applying our proprietary KinetiSol technology to help enhance the bioavailability of one of these promising drug candidates," said Dr. Edward Rudnic, CEO of DisperSol Technologies. "This collaboration is another example of our partnering strategy with our KinetiSol technology platform to help improve the bioavailability of next generation targeted therapies to provide new treatments for patients in need."

On December 17, 2021 Deep Lens and Ventura County Hematology Oncology Specialists reported that they have entered into a strategic agreement that will expand clinical trial opportunities for patients in the Ventura county area (Press release, Deep Lens, DEC 17, 2021, View Source [SID1234597436]). As part of this collaboration, Ventura County Hematology Oncology Specialists will integrate Deep Lens’ artificial intelligence (AI) based clinical trial matching solution and other services to identify patients for trials faster and more effectively. Ventura County Hematology Oncology Specialists is a comprehensive cancer center serving patients across Ventura and the surrounding coastal communities. Deep Lens is a digital healthcare company that leverages AI to improve inefficiencies in the oncology clinical trial recruitment process.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our clinical trial program is an integral part of our overall offering to patients, as we believe that everyone should have access to novel therapies in development that have the potential to change the course of their disease," said Lynn Kong, MD, of Ventura County Hematology Oncology Specialists. "However, as many new therapies have become increasingly more targeted to address specific markers or mutations, the trials to support them have become more complex. Unfortunately, this means that identifying patients for trials is more labor intensive and timelines are often shortened, making it difficult for staff to enroll the right patients at the right time. We look forward to leveraging Deep Lens’ technology and services so that we can continue to provide our patients with every resource possible to treat their disease."

More than 15,000 oncology clinical trials are actively recruiting patients; however, fewer than 1 in 30 patients participate in a clinical trial. Limited trial site resources make it time-consuming to identify eligible patients, especially as trial protocols increase in complexity. Deep Lens supports care teams by automating the identification of potentially eligible patients at the time of diagnosis and easily matching them to relevant trials.

"We are thrilled to welcome the Ventura team into our network of community-based oncology practices. The majority of patients diagnosed with cancer are treated by community oncologists, and it is critical to bring more trials to this setting so that patients can receive access to novel therapies in a comfortable, familiar environment, without having to travel or commute to larger medical centers," said Tyrone Richardson, vice president, provider sales at Deep Lens. "Ventura is a great example of a community oncology practice that prioritizes clinical research and we’re delighted that we can add value to their program and help more of their patients receive stellar, cutting- edge care."

Deep Lens’ software will pre-screen patients from Ventura County Hematology Oncology Specialists’ EMR (OncoEMR) and integrate molecular data feeds from Guardant Health and Foundation Medicine, as well as all pathology feeds to automatically identify qualified patients for clinical trials. Deep Lens’ pre-screening and clinical trial matching solution is provided at no cost to oncology practices.

Deep Lens is working with a significant number of community oncology practices representing every region in the U.S. It is estimated that approximately 85 percent of cancer patients are diagnosed and treated at local, community-based oncology practices. Deep Lens is committed to expanding important oncology research by making trials more accessible to a larger and more diverse population within these local community settings.