Galera Has Novel Radiation Oncology Pipeline; Commercialization Looms

Galera Therapeutics Inc (NASDAQ: GRTX), a biopharma company that is working on novel therapeutics for transforming radiotherapy treatment in cancer, recently IPO’d, offering 5 million shares at $12 apiece.

Following the expiry of the IPO quiet period, Citigroup analyst Yigal Nochomovitz initiated coverage of Galera with a Buy rating and $20 price target.

Credit Suisse analyst Evan Seigerman initiated coverage of the shares with a Neutral rating and $14 price target.

New Player with a Novel Approach In Radiation Oncology Market

Galera has demonstrated very good proof-of-concept Phase 2b data for lead drug GC4419 in the prevention of severe oral mucositis – a radiation side effect common in head and neck cancer, Nochomovitz said in a note.

The analyst assigned a 80% probability of the FDA approving GC4419 for he indication, with the pipeline asset most likely to become standard-of-care.

Nochomovitz also expects positive readthrough for GC4419 in a second indication – esophagitis in lung cancer.

“We see potential upside for second asset GC4711 if initial proof-of-concept data in locally-advanced pancreatic cancer (LAPC) are positive,” Citi said in the note.

The firm estimates peak risk-adjusted revenues of $370 million for oral mucositis, $200 million for esophagitis and $9 million for LAPC.

Commercialization Faces Significant Challenges

Galera’s lead asset GC4419, an intravenous administered, small molecule dismutase mimetic currently in Phase 3 development for oral mucositis, addresses an unmet need with differentiated efficacy, but there are likely to be headwinds to broad commercialization due to pipeline competition and logistical challenges, Seigerman said.

The analyst expects the pivotal Phase 3 data from the ROMAN study to be positive, supporting approval by 2023. Commercial launch is likely by 2023, with the asset estimated to rake in unadjusted peak sales of over $200 million by 2025.

With GC4419 required to be administered as a 60-minute infusion immediately prior to radiation, the analyst sees only a limited number of facilities as capable of offering the IV infusion as well as radiation.

“We see a favorable risk/reward for the early pipeline for esophagitis and anti-cancer efficacy improvement, but the path to commercialization remains unclear, Credit Suisse wrote in the note.

Therefore, the firm said it is assigning no value to indications outside of oral mucositis, although it sees upside to its forecast stemming from pipeline progress.

https://www.benzinga.com/analyst-ratings/analyst-color/19/12/14913617/analysts-galera-has-novel-pipeline-for-radiation-oncology-market-commercialization-

Olaparib first gene-targeted medicine to show benefits in prostate cancer

A pioneering precision medicine already licensed for breast and ovarian cancer can also slow or stop tumour growth in some men with advanced prostate cancer, a new clinical trial shows.

The phase II trial found that over 80 per cent of men with prostate cancer whose tumours had mutations in the BRCA genes responded well to treatment with the targeted drug olaparib.

Men in the study had already received chemotherapy and their disease was advanced. Patients treated with olaparib whose prostate cancers had DNA repair defects lived for more than 13 months on average – and nearly 18 months among those with BRCA mutations – raising the prospect that it could become the first ever gene-targeted drug to be approved for prostate cancer.

The TOPARP-B trial was led by a team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust. It is published in The Lancet Oncology today (Friday) and was funded in part by olaparib’s manufacturer, AstraZeneca, plus by Cancer Research UK, Prostate Cancer UK, the Prostate Cancer Foundation, Movember and the Experimental Cancer Medicine Centre (ECMC) Network.

An initial trial, TOPARP-A, tested use of olaparib in a group of men with advanced prostate cancer who weren’t selected for treatment based on gene mutations, and suggested that those whose tumours had mutations in a range of genes involved in repairing damage to DNA could benefit most.

That led to TOPARP-B, which was the first study to direct olaparib specifically at men whose prostate cancers had mutations in their DNA repair systems. The researchers used olaparib to treat 98 men, at 17 UK hospitals, with mutations in DNA repair genes, and who all had advanced cancer which had been heavily pre-treated. Overall, they found that 47 per cent of men with these DNA repair defects responded to olaparib, halting disease progression for an average of 5.5 months.

The most common DNA repair defects were mutations in the BRCA1 and BRCA2 genes, but various other mutations were also detected including those in the PALB2, ATM and CDK12 genes.

Men with BRCA mutations responded best to olaparib, with more than 80 per cent responding and 40 per cent remaining free of disease progression for more than a year. Additionally, over half of patients carrying PALB2 mutations responded to olaparib, as well as 37 per cent of those with ATM mutations. Some 20 per cent of patients with other DNA repair gene alterations also responded to olaparib.

The median overall survival with olaparib was 17.7 months for patients with BRCA mutations, compared with 16.6 for men with ATM mutations, and 13.9 months for those with PALB2 mutations.

Olaparib is one of a class of drugs called PARP inhibitors which are licensed for women with ovarian and breast cancer who have mutations in the BRCA genes. Scientists at The Institute of Cancer Research (ICR) were the first to discover how to genetically target olaparib, and they went on to develop the drug in clinical trials with colleagues at The Royal Marsden.

The researchers believe men with advanced prostate cancer should now routinely have their tumours tested for DNA repair defects such as BRCA mutations, so that where appropriate they can benefit from PARP inhibitors.

The ICR is seeking to discover novel gene-targeted medicines and innovative ways of combining them within its pioneering new Centre for Cancer Drug Discovery – a £75 million investment focused on finding new ‘anti-evolution’ treatments that can overcome drug resistance.

Study leader Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:

“Our trial has shown that men with prostate cancer who were selected for faults in DNA repair genes responded very well to the targeted drug olaparib, especially where they had BRCA mutations in their tumours.

“This study and another phase III trial place olaparib on the verge of becoming the first genetically targeted treatment in prostate cancer. I’m excited by these findings, and keen to see further research assessing how we can combine olaparib with other treatments to extend patients’ lives even more dramatically.”

Professor Paul Workman, Chief Executive at The Institute of Cancer Research, London, said:

“Precision medicines targeted to specific genetic faults are transforming treatment for many different cancers, and with this new research it looks like we will soon be able to add prostate cancer to that list. It’s exciting to see a drug which the ICR helped pioneer having such widespread benefits for both women and men with cancer.

“The next step is to work out how to combine olaparib with other drugs to keep cancer at bay for much longer. That’s the kind of research we will be carrying out in our new Centre for Cancer Drug Discovery, which aims to create innovative new treatments designed to overcome cancer evolution and drug resistance.”

https://www.eurekalert.org/pub_releases/2019-12/iocr-obf112919.php

Canaccord Initiates Coverage on Galmed at Buy

Canaccord Genuity started coverage on shares of Galmed Pharmaceuticals (NASDAQ:GLMD) in a report released on Monday. The firm set a “buy” rating on the biopharmaceutical company’s stock.

Canaccord Genuity Initiates Coverage on Galmed Pharmaceuticals (NASDAQ:GLMD)

Amazon’s new medical transcription service bolsters voice-to-text bid

• Amazon Web Services unveiled a medical speech recognition service that converts doctor-patient conversations to text in a bid to streamline onerous clinical documentation and lower administrative costs.
• Called Amazon Transcribe Medical, the product is HIPAA-eligible and integrates into voice-enabled applications and microphones via an application programming interface. It was developed in partnership with AWS clients, including EHR giant Cerner and voice-enabled clinical assistant company Suki, and announced Monday during AWS’ annual conference in Las Vegas.
• AWS’ seven HIPAA-eligible offerings already included Amazon Transcribe, a speech-to-text service, but Transcribe Medical has a higher level of accuracy in recognizing healthcare-specific words and medical terminology, according to the company.

Amazon is among the big tech names working to dominate the lucrative voice-to-text market, including Google and Microsoft, two cloud giants that also operate speech assistants taking notes in real time. Microsoft is developing ambient sensing technology with clinical documentation company Nuance, focusing on how to automatically input health data into the correct spot in the EHR.

Google has been working with Stanford University for two years on transcription of medical conversations. Additionally Suki, which worked with AWS to develop Transcribe Medical, has an ongoing partnership with Google Cloud, though CEO Punit Soni told Healthcare Dive in October it’s not an exclusive relationship.

Amazon and other non-traditional entrants are looking to diversify revenue streams to bolster their bottom lines. Amazon saw its profit fall year over year in the third quarter for the first time since 2017, but AWS continued to be a major profit driver with operating income of $2.26 billion in the quarter, almost 72% of Amazon’s total operating profit.

The problem of administration overload is well known: Clinicians can spend up to an average of six hours per day writing notes for EHR data entry alone. Several startups and established players, including Amazon, are working on ways to ameliorate the documentation workflow, which is full of repetitive typing and routine actions that can be automated.

Unlike some other early end-to-end offerings, Transcribe Medical does not automatically insert relevant personal health information into a patient’s EHR. However, according to AWS, the new service still saves time in medical data entry and can be used in tandem with Amazon Comprehend Medical, the e-commerce giant’s text analytics software, to find patterns in medical text to suggest diagnoses, treatments and more.

The software isn’t just targeted to providers. Cerner uses the digital voice scribe to transcribe clinician-patient interactions, then ties in its own artificial intelligence software to enter data into the correct slot in its EHR. And biotech giant Amgen has already used Transcribe Medical to review recorded calls from patients and providers to identify potential side effects of its drugs.

Amazon linked with Cerner in July to develop artificial intelligence and machine learning products in an expansion of an existing partnership. The two hinted Amazon’s voice recognition and natural language processing capabilities would impact Cerner’s tech offerings at the time.

AWS does not collect or use patient’s health information for research and development under the terms of its business associate agreements with health customers, a fact the company explicitly laid out amid an unfriendly environment concerned about big tech’s involvement in healthcare and its privacy implications.

https://www.healthcaredive.com/news/amazons-new-medical-transcription-service-bolsters-voice-to-text-bid/568245/

Stem cell therapy shows promise for the first time in spinal cord injury

Researchers have published the results of their work where stem cell therapy has shown promise in a case of spinal cord injury. The results of their case study were published in the latest issue of the journal Mayo Clinic Proceedings last week. The study was titled, “Celltop Clinical Trial: First Report From a Phase I Trial of Autologous Adipose-Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury.”

This was essentially the first case and a Phase I clinical trial to see the safety of the procedure said Mohamad Bydon, a Mayo Clinic neurologic surgeon and the lead author of the study. The team used mesenchymal stem cell treatment for the patient and they added a warning that not all patients may show the same levels of success as this case. Dr. Bydon explained, “While in this case, the first subject was a super-responder, others may not respond in the same manner. We do not yet understand all of the necessary biology needed to achieve neurological recovery in paralyzed individuals. One of our objectives in this study and future studies is to better delineate who will be a responder and why patients respond differently.”

The team wrote that over 17000 persons in the United States suffer from traumatic spinal cord injury annually and the burden of the injuries affect 291,000 or more annually. These injuries thus form a major socioeconomic burden and cost the health care system over $40 billion including the loss as work force. Regenerative medicine using stem cells have been one avenue that has been explored in the recent years to seek for answers to paralysis caused due to spinal cord injuries. The team wrote that the, “adipose tissue represents a readily accessible and viable source of MSCs. Available evidence has shown that adipose tissue derived (AD) MSCs can regulate inflammatory responses and provide a regeneration-permissive environment in animal models of SCI.”

This trial, the team wrote, was planned with 10 patients who were paralyzed as a result of traumatic spinal cord injury (SCI). Mesenchymal stem cell therapy was tried on the patients and one of them showed motor as well as sensory benefits from the therapy and did not show any side effects of adverse reactions. They wrote,” The CELLTOP study, an ongoing multidisciplinary phase 1 clinical trial conducted at Mayo Clinic (ClinicalTrials.gov Identifier: NCT03308565), is investigating the safety and efficacy of intrathecal autologous AD-MSCs in patients with blunt, traumatic SCI.” (AD MSCs – Adipose tissue derived mesenchymal stem cells).

The patient, 53 year old man, Chris Barr, said that he had never hoped to regain motor or sensory functions after his surfing accident. In his recent interview to the media he has said, “The prognosis was — was bad… And bad meaning, you know, probably a 95 to 97 percent chance that I’ll have nothing below my neck.” His injury was labelled as “American Spinal Injury Association Impairment Scale grade A”.

For this procedure where he was the first to sign up, he underwent stem cell therapy which had never been tried before. Stem cells were taken from his own body and in the lab they were coaxed into turning into becoming spine cells. These stem cells were derived from the adipose tissues or fat cells. Authors wrote that “100 million autologous AD-MSCs” were then injected back into his spinal cord at the level of the lumbar spine. This was done 11 months after the spinal injury Barr suffered. With regular physiotherapy after the treatment, Barr has regained his senses in the lower limbs and can walk on his own feet, explain the researchers. The patients was tested for any side effects at 3, 6, 12 and 18 months after the injection of the stem cells to his spine.

Authors wrote in conclusion, “Thus, in this treated individual with SCI, intrathecal administration of AD-MSCs was feasible and safe and suggested meaningful signs of improved, rather than stabilized, neurologic status warranting further clinical evaluation.”

According to Dr. Bydon, despite the fact that not all may respond similarly, this study spkrks hope among hundreds of thousands of individuals who suffer from traumatic spinal cord injuries each year and remain paralyzed for life. Bydon said, “The hope is that we will have novel treatments for spinal cord injuries in the coming years that will be different from what we have today. These will be therapies that do not rely upon supportive care, but therapies that rely on science to create a regenerative process for the spinal cord.”

Journal reference:

CELLTOP Clinical Trial: First Report From a Phase 1 Trial of Autologous Adipose Tissue–Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury Bydon, Mohamad et al. Mayo Clinic Proceedings, https://www.mayoclinicproceedings.org/article/S0025-6196(19)30871-7/fulltext

https://www.news-medical.net/news/20191202/Stem-cell-therapy-shows-promise-for-the-first-time-in-spinal-cord-injury.aspx

Astellas Pharma to buy Audentes Therapeutics for $60/share

Audentes Therapeutics (NASDAQ:BOLD) agrees to be acquired by Astellas Pharma (OTCPK:ALPMF) for US$60/share in cash, representing a total equity value of ~US$3B; shares are halted.

https://seekingalpha.com/news/3523217-astellas-pharma-buy-audentes-therapeutics-60-share

‘Clever drugs for slimy bugs’ in fight against staph infections

Eradicating deadly staph using a new breed of antibiotics has revealed promising results in research released by Queensland University of Technology, to help overcome one of the biggest modern medical challenges.

The bacteria attach to medical devices including catheters, artificial joints, implants and patients’ burns and wounds, establishing bacterial biofilms, a leading cause of failing antibiotic therapies and chronic infections.

QUT researchers have developed hybrid antibiotics designed to penetrate the slimy shield protecting invasive golden staph (Staphylococcus aureus) infections.

Led by Associate Professor Makrina Totsika and PhD student Anthony Verderosa, the research has been published in top infectious diseases journal Antimicrobial Agents and Chemotherapy.

The study found hybrid antibiotics worked well by destroying Staph biofilms grown in the lab.

“Biofilms are a sticky, slimy coating that often prevents conventional antibiotics from accessing bacterial cells,” Mr Verderosa said.

“We have developed a new breed of antibiotic that tricks biofilms into releasing their protected cells allowing access through the protective slimy coating of the biofilm.

“This allows for the biofilms to be eradicated.”

The PhD student and a recipient of a medal for his QUT Applied Science honours degree in chemistry described the new antibiotics as “clever drugs for slimy bugs.”

He said the microscopic compound emits a fluorescence signal enabling researchers to watch the drug penetrating the biofilm, either killing the bacteria directly or leaving them susceptible to killing.

Associate Professor Totsika said the majority of infections, even those not associated with an implanted medical device, involve biofilms in some way so the potential for these drugs is wide.

“We are now gearing up to do pre-clinical testing,” she said.

“What is promising is the fact that our compounds are hybrids of drugs that are already in clinical use as stand-alone therapies, such as conventional antibiotics and nitroxides, so this offers hope that they could be translated into clinical therapies in the not so distant future.”

Hospital acquired infections and increasing resistance to antibiotics has challenged medical researchers to find and test novel antimicrobial agents, including alternatives to antibiotics.

The World Health Organisation has identified antibiotic resistant pathogens as one of the “biggest threats to global health today.”

Associate Professor Totsika said there was scope to apply the research beyond medicine, to agriculture, biotechnology and other industries.

She is the recipient of a QUT Vice-Chancellor’s Research Fellowship, and her research is supported by grants from the National Health and Medical Research Council and the Australian Research Council.

Researchers involved in developing the hybrid antibiotics came together from QUT’s Infection and Immunity Research Program as well as the Molecular Design and Synthesis Chemistry program.

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Story Source:

Materials provided by Queensland University of Technology. Note: Content may be edited for style and length.

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Journal Reference:

1. Anthony D. Verderosa, Rabeb Dhouib, Kathryn E. Fairfull-Smith, Makrina Totsika. Nitroxide functionalized antibiotics are promising eradication agents against Staphylococcus aureus biofilms.. Antimicrobial Agents and Chemotherapy, 2019; DOI: 10.1128/AAC.01685-19

https://www.sciencedaily.com/releases/2019/12/191202112956.htm