On June 30, 2022 Race Oncology Limited ("Race") reported to share further interim results from our preclinical cardioprotection program in collaboration with researchers from the University of Newcastle (ASX announcement: 28 April 2021) (Press release, Race Oncology, JUN 30, 2022, View Source [SID1234616398]). This program aimed at exploring the use of Zantrene (bisantrene dihydrochloride) as a cardioprotective agent which offered synergy with anti-cancer treatments.

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Zantrene was found to protect the hearts of mice from the damaging effects of anthracyclines (specifically doxorubicin) even when the chemotherapeutic dose was increased without significant additional toxicity or bone marrow suppression.

On June 30, 2022 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported the initiation of a clinical study of LYT-100 (deupirfenidone), PureTech’s wholly-owned therapeutic candidate for the potential treatment of idiopathic pulmonary fibrosis (IPF), to support its registration-enabling package (Press release, PureTech Health, JUN 30, 2022, View Source [SID1234616397]). LYT-100 is a selectively deuterated form of pirfenidone. Pirfenidone is a proven therapy for IPF, a devastating condition where the favorable tolerability, safety and potentially higher exposure of LYT-100 could have an important impact on patient adherence and outcomes.

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"The initiation of this study is supported by substantial clinical data demonstrating favorable safety and tolerability of LYT-100," said Julie Krop, M.D., Chief Medical Officer of PureTech. "The unique profile of LYT-100, coupled with the established efficacy of pirfenidone, has the potential to significantly improve care for these patients. We believe that enabling patients to stay on a therapeutic dose longer – even at a dose with comparable exposure to the FDA-approved dose of pirfenidone – has the potential to drive better efficacy. In addition, achieving higher exposure levels than the FDA-approved dose of pirfenidone has the potential to offer even better efficacy, which is our rationale for pursuing a higher dose of LYT-100 in this study. We are excited to be taking this important step towards our goal of helping patients with this devastating condition."

IPF is a chronic orphan condition that causes progressive scarring of the lungs, and approximately 130,000 people in the U.S. are living with the disease. The prognosis of IPF is poor, with the median survival after diagnosis generally estimated at two to five years. Pirfenidone is approved by the U.S. Food and Drug Administration (FDA) for IPF, yet there are serious limitations to pirfenidone’s clinical use, primarily due to severe gastrointestinal (GI)-related tolerability issues.1,2

"Pirfenidone has proven efficacy to slow the decline in lung function in patients with IPF. However, many patients with IPF who start pirfenidone have side effects that cause them to either discontinue therapy or reduce their dose," said Kevin Flaherty, M.D., Professor of Internal Medicine at the University of Michigan specializing in IPF and other interstitial lung diseases and an advisor to PureTech. "I am excited by the safety and tolerability data generated to date with LYT-100, particularly the most recent data demonstrating how well-tolerated it was in a relatively sick, older patient population with multiple comorbidities, as I believe it could represent great potential in patients with IPF."

LYT-100 is designed to retain the potent and clinically validated anti-fibrotic and anti-inflammatory activity of pirfenidone but has demonstrated a highly differentiated pharmacokinetic (PK) profile that has translated into improved tolerability in PureTech’s ongoing clinical development program. To date, LYT-100 has been studied in more than 400 subjects and demonstrated a favorable safety and tolerability profile. In a crossover study in healthy older adults with similar median age to patients with IPF, PureTech showed that approximately 50% fewer subjects experienced GI-related adverse events (AEs) with LYT-100 compared with pirfenidone (17.4% vs. 34.0%) and substantially fewer subjects experienced AEs with LYT-100 vs. pirfenidone. PureTech also recently showed that LYT-100 can be safely dosed with a higher total drug exposure than the currently approved dose of pirfenidone, which could translate into improved efficacy over pirfenidone.

The global, randomized, placebo-controlled registration-enabling study is designed to evaluate the efficacy, tolerability, safety and dosing regimen of LYT-100 to help inform the study design for a potential pivotal study and to assess the relative efficacy of LYT-100 compared to pirfenidone. A total of approximately 240 patients will be randomized 1:1:1:1 to receive either one of two dose levels of LYT-100, the FDA-approved dose of pirfenidone, or a placebo. One of the LYT-100 arms will evaluate 550 mg three times a day (TID) of LYT-100, which has previously demonstrated the comparable exposure as the currently approved dose of pirfenidone (801 mg TID), and the other arm will evaluate an 825 mg TID dose of LYT-100, which has demonstrated higher exposure than the currently approved dose of pirfenidone with the potential for improved efficacy. The primary objective of the study is to demonstrate a statistically significant and clinically meaningful difference in the slope of decline in a measure of lung function, Forced Vital Capacity (FVC), in the LYT-100 treatment arms compared to placebo over 6 months. The study will also evaluate safety, tolerability and the slope of FVC decline in the LYT-100 treatment arms compared to pirfenidone, though this analysis is not powered to demonstrate strict non-inferiority. FVC is an established measure of pulmonary function in IPF and has served as the basis for FDA approval of the currently marketed treatments for IPF. Topline results from the study are expected by the end of 2023.

Advancement of LYT-200 Clinical Program

PureTech’s LYT-200 program is also progressing through clinical development. Following the completion of the monotherapy dose escalation portion of the Phase 1 program, PureTech has begun to evaluate weekly doses of LYT-200 and will soon begin to enroll patients in cohorts designed to evaluate LYT-200 in combination with chemotherapy or an anti-PD-1 monoclonal antibody. Results from the single agent cohorts are expected by the end of 2022, and results from the combination cohorts are expected in 2023.

LYT-200 is a fully human IgG4 monoclonal antibody (mAb) designed to inhibit the activity of galectin-9, a key molecule expressed by tumors and immune cells and shown in preclinical models to suppress the immune system from recognizing and destroying cancer cells. The primary objective of the Phase 1 portion of the ongoing adaptive Phase 1/2 study is to assess the safety and tolerability of escalating doses of LYT-200 in order to identify an appropriate dose and dosing interval to carry forward into the Phase 2 portion of the trial. Six cohorts were treated with escalating, bi-monthly doses from 0.2-16 mg/kg, and no dose limiting toxicities were reported to date.

Additionally, compelling preclinical data have been generated with LYT-200 in leukemia models, which will be submitted for presentation in a scientific forum. Based on these data, PureTech plans to initiate a study of LYT-200 as a single agent in leukemia patients by the end of 2022.

"We are very pleased with the progress of our Phase 1 evaluation of LYT-200, which has demonstrated favorable safety and tolerability as a single agent at all doses studied to date without any dose limiting toxicities," said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech. "We look forward to the continued evaluation of this novel therapy as a potential treatment for metastatic solid tumors as well as the initiation of clinical studies in leukemia."

About LYT-100

LYT-100 is one of seven therapeutic candidates within PureTech’s Wholly Owned Pipeline. It is a selectively deuterated form of pirfenidone that is designed to retain the potent and clinically-validated anti-fibrotic and anti-inflammatory activity of pirfenidone with a differentiated pharmacokinetic profile that has translated into favorable tolerability, as supported by data from multiple human clinical studies. LYT-100 is being advanced for the potential treatment of conditions involving inflammation and fibrosis, including idiopathic pulmonary fibrosis and breast cancer-related, upper limb secondary lymphedema. PureTech is also exploring the potential evaluation of LYT-100 in other inflammatory and fibrotic conditions such as myocardial and other organ system fibrosis based on the strength of existing clinical data around the use of pirfenidone in these indications.

About LYT-200

LYT-200 is a fully human IgG4 monoclonal antibody targeting a foundational immunosuppressive protein, galectin-9, for the potential treatment of solid tumors, including pancreatic ductal adenocarcinoma, colorectal cancer and cholangiocarcinoma, that are difficult to treat and have poor survival rates. PureTech has presented preclinical data demonstrating high expression of galectin-9 across breast cancer, pancreatic and cholangiocarcinoma samples and found that the highest levels of galectin-9 correlated with shorter time to disease relapse and poor survival. These data suggest that galectin-9 could be significant both as a therapeutic target for a range of cancers and as a cancer biomarker. Preclinical animal and patient-derived organoid tumor models also showed the potential efficacy of LYT-200 and the importance of galectin-9 as a target. LYT-200 is currently being evaluated in a Phase 1/2 adaptive design trial.

On June 30, 2022 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported an update on recent progress with its two pipeline assets, paxalisib and EVT801, and on recent corporate financing activity (Press release, Kazia Therapeutics, JUN 30, 2022, View Source [SID1234616396]).

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Key Points

EVT801 phase I study protocol has cleared third dose level and is recruiting well.

GBM AGILE pivotal study has opened in France, the fourth country to commence recruitment to the paxalisib arm.

Phase I study of paxalisib in combination with radiotherapy for treatment of brain metastases at Memorial Sloan Kettering Cancer Center has been accepted for presentation at an upcoming academic conference in Q3 CY2022.

ATM financing facility has realized gross proceeds of US$ 2,956,036 for the period ending June 2022, at an average price of $6.08 (approximately AU$ 0.88 per share).

Kazia CEO, Dr James Garner, commented, "Despite a challenging first half equity market for biotech companies, Kazia has continued to make good progress. The GBM AGILE pivotal study is progressing well, and appears on track for data in 2H CY2023, as anticipated. We have been pleased in the first half to see new data presented and milestones delivered from several projects, and we expect that pace to continue and increase during the second half."

EVT801 Phase I Study

The phase I study of EVT801 in patients with advanced cancer continues to recruit well. The drug has recently completed the third of a potential eight dose levels and is anticipated to open recruitment to the fourth dose cohort in the near future. To date, the drug appears generally well-tolerated. Depending on how many dose cohorts are required to establish a maximum tolerated dose (MTD), interim data from the study is anticipated in 2H CY2022 or 1H CY2023.

GBM AGILE

More than forty sites are currently open to the paxalisib arm of GBM AGILE. The first site to commence recruitment to the paxalisib arm in France opened in June 2022, making France the fourth country to join the study, alongside the United States, Canada, and Switzerland.

In January 2022, the Global Coalition for Adaptive Research (GCAR), the sponsor of GBM AGILE, stated that over a thousand patients had been screened to the study, with enrolment rates approximating 0.75 to 1.00 patients per site per month, which is around four times higher than would generally be expected in a clinical study of glioblastoma.

Kazia continues to work closely with GCAR and Simcere Pharmaceutical to open the study in China. Public health measures in some Chinese cities relating to the ongoing COVID pandemic have had a modest impact on operational activities, but it is currently anticipated that the study will open in China during 3Q CY2022.

Paxalisib in Brain Metastases

In June 2022, the company announced that a multi-drug, genomically-guided study in brain metastases run by the Alliance for Clinical Trials in Oncology had seen the paxalisib arm graduate to an expansion cohort in patients with breast cancer brain metastases, having seen positive efficacy signals in the initial exploratory cohort. Paxalisib continues to recruit to the exploratory cohort in two other patient subgroups.

Interim data from a phase I study of paxalisib in combination with radiotherapy for patients with brain metastases run by Memorial Sloan Kettering Cancer Center has been accepted for an oral presentation at an upcoming international conference in Q3 CY2022. Kazia looks forward to sharing data from this presentation as soon as it is available.

Financing

In May 2022, Kazia established a NASDAQ-based at-the-market financing facility with Oppenheimer and Company. For the period ending June 30, 2022, the company has issued 486,281 American Depository Shares (ADSs) under this facility, at an average price of $6.08, for total gross proceeds of US$ 2,956,036 (approximately AU$ 4,256,691). Of note, these shares have been issued at no discount, with no warrant coverage, and with transaction fees approximately half of those associated with traditional financing.

On June 30, 2022 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas" ), Nitto Denko Corporation (TSE: 6988, President: Hideo Takasaki, "Nitto"), and M. Heart Co., Ltd. (President and CEO: Yoshimi Mizunuma, "M. Heart") reported that the three companies have entered into an agreement for a sales pilot of disposable Holter ECG device "EG HolterTM" for the Japan market (Press release, Astellas, JUN 30, 2022, View Source [SID1234616392]). Based on this agreement, Astellas has established an e-commerce site for healthcare professionals and will start the sales pilot of the device today.

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This is Astellas’ first initiative in Rx+ program to promote a product through an e-commerce site. After verifying the business model through the sales pilot, Astellas will move to full-scale marketing of the product.

EG Holter is a holter electrocardiograph designed and developed by Nitto. Because it is a disposable device, it is hygienic and does not require maintenance. It is 6 mm thick,11 g in weight, has no cords, and is water resistance (IPX4). It is easy to attach and remove.

Data obtained by EG Holter will be analyzed by "MYHOLTER II", which is software for the holter analyzer jointly developed by Astellas and M. Heart. MYHOLTER II is a program that analyzes holter ECG data with a proprietary analytical algorithm using artificial intelligence (AI). M. Heart has obtained cerification for EG Holter and MYHOLTER II as medical device (Class II).

Astellas, Nitto and M. Heart have come together to create a simple, convenient, patient-centered solution for patients and medical institutions.

Medical costs for heart diseases and other cardiovascular diseases in Japan exceed 6 trillion yen per year―the highest of any disease category1. Of particular concern is cardiogenic cerebral embolism, which occurs when a thrombus that formed in the heart blocks an artery in the brain or neck. This has a high mortality rate (20%) and often results in severe sequelae, such as a bedridden state (40%)2. Atrial fibrillation is said to be the cause of cardiogenic cerebral embolism in 3 out of 4 cases2. Early detection of atrial fibrillation is an important social issue.

By providing a total solution that involves combining convenient ECG testing using the EG Holter and the data analysis using MYHOLTER II, Astellas, Nitto, and M. Heart propose to enable early detection and appropriate treatment of atrial fibrillation, a condition estimated to affect approximately 700,000 patients in Japan2, and contribute to the prolongation of healthy life expectancy.

On June 29, 2022 ReCode Therapeutics, a genetic medicines company using superior delivery to power the next wave of messenger RNA (mRNA) and gene correction therapeutics, reported the close of a Series B extension financing round, co-led by new investors, Leaps by Bayer, the impact investment unit of Bayer AG, AyurMaya, an affiliate of Matrix Capital Management, and with participation from Amgen Ventures (Press release, ReCode Therapeutics, JUN 29, 2022, View Source;utm_medium=rss&utm_campaign=recode-therapeutics-to-expand-next-generation-delivery-platform-and-diversify-genetic-medicines-pipeline-with-oversubscribed-series-b-financing-totaling-200m [SID1234619533]). With the additional $120M in new financing, the company has secured a total of $200M in Series B funding. In connection with the financing, Alan Colowick, M.D., M.P.H., managing director of Matrix, and Rakhshita Dhar, senior director of Venture investments Health at Leaps by Bayer, will join ReCode’s Board of Directors.

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"At AyurMaya, we help build companies that have the potential to transform the therapeutic landscape for patients. ReCode has an impressive combination of groundbreaking science, a highly accomplished leadership team and investor base, and the opportunity to have an immense impact on accelerating precision genetic medicines through delivery to disease-relevant cells," said Alan Colowick, M.D., M.P.H, Matrix Capital Management. "I am delighted to join ReCode’s Board during this important growth trajectory for the company and am eager to work with the leadership team to expand ReCode’s next generation genetic medicines delivery platform and diversify its pipeline."

The initial Series B financing announced in October 2021 was co-led by Pfizer Ventures and EcoR1 Capital and included Sanofi Ventures, Orbimed, Vida Ventures, MPM Capital, Colt Ventures, Hunt Technology Ventures L.P., Osage University Partners, Tekla Capital Management LLC, Superstring Capital, and NS Investment. Proceeds from the financing will be used to fund the diversification of ReCode’s pipeline into central nervous system (CNS), liver, and oncology indications, while continuing to advance ReCode’s lead mRNA programs for primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) into the clinic. The funds also will be used to advance development of ReCode’s platform to deliver a wider range of genetic medicine cargoes, including additional gene correction modalities and small interfering RNA (siRNA) therapies, to a wider range of target cell types in a predictable and programmable fashion.

"The successful administration of billions of doses of mRNA COVID-19 vaccines, and continued progress with novel RNA and gene correction therapeutics, have catapulted us into a new era of possibility for genetic medicines. We are harnessing that potential with our novel selective organ targeting (SORT) lipid nanoparticle (LNP) delivery platform which is engineered with unique properties to enable delivery of genetic therapeutics directly to the organs and cells most impacted by disease, offering improved efficacy and potency. This potentially game-changing precision medicine technology creates vast possibilities for genetic medicines which have been limited by current technologies," said Shehnaaz Suliman, M.D., MBA, M.Phil., chief executive officer and board member, ReCode Therapeutics. "With the infusion of new capital and the addition of AyurMaya, an affiliate of Matrix Capital Management, and Leaps by Bayer to our high-caliber board, we are confident that our team will successfully drive ReCode’s mission to develop new precision genetic medicines enabled by superior delivery."

The capability to precisely target specific organs and cell types is important for maximizing the efficacy of genetic medicines and limiting potential adverse effects. Additionally, as evidenced with the mRNA COVID vaccines and novel RNA and gene correction therapeutics, LNP packaging enables redosing. For people with genetic diseases such as CF that require potentially lifelong therapy, this means LNP delivered therapeutics can be administered repeatedly over time, potentially without significant immunogenicity.

"The ability to directly target specific organs and cells beyond the liver remains a key challenge for genetic medicines," said Juergen Eckhardt, head of Leaps by Bayer. "At Leaps by Bayer, we strongly focus on finding breakthrough solutions that have the potential to make a meaningful difference for people with rare genetic diseases, and we believe ReCode is a unique company in our industry whose innovations have the potential to fundamentally shift an entire area of genetic medicine."

In May 2022, ReCode presented preclinical data from its two lead programs in PCD and CF at the American Thoracic Society (ATS) 2022 International Conference. These data demonstrated that selective organ targeting (SORT) LNP-formulated therapeutic candidates for PCD and CF can be precisely delivered directly to disease-relevant cells without significant exposure to other tissue, effectively releasing the encapsulated genetic cargo, and expressing the correct proteins at relevant levels. The company plans to advance to investigational new drug (IND) filings for PCD and CF in late 2022 and mid-2023, respectively.

About the SORT LNP Platform

ReCode is differentiated by its first-in-class modular genetic medicines delivery platform. The company’s selective organ targeting (SORT) lipid nanoparticle technology (LNP) platform is the foundation for its pipeline. Pioneered by co-founder Professor Daniel J. Siegwart, Ph.D., of the University of Texas, and described by Nature as one of the "Seven Technologies to Watch in 2022," ReCode’s SORT LNP platform is an innovation beyond the lipid delivery system used by the mRNA COVID vaccines and novel RNA and gene correction therapeutics.

LNPs are used to package and deliver genetic cargo such as mRNA. When delivered into the blood, first-generation LNPs primarily are taken up by the liver, which limits their utility for broad therapeutic applications. ReCode’s SORT LNPs are engineered with a biochemically distinct fifth lipid to help the body "sort" and direct the LNPs to other targeted organs such as the lung and spleen, with the ability to bypass the liver, if desired.

Beyond its highly selective targeting capability, ReCode’s SORT LNP platform is further distinguished by its versatility in both mode of administration (including IV, inhaled, subcutaneous, intramuscular, and intrathecal), and the diversity of genetic cargo that can be delivered (including mRNA, siRNA, DNA, gene correction components and mixed cargoes). Together, these qualities offer vast opportunities to address a wide range of unmet medical needs through a precision medicine approach that delivers the right medicine to the right organs and cells using the optimal mode of administration.