Secretive Sana, still a year away from clinic, files for IPO after huge raise

 Sana Biotechnology is following the Moderna playbook to a tee: Promise a lot based on very early science, be vague, nab a major VC raise, then gun for an IPO.

While Moderna has, in some respects, come up good after its monster $600 million-plus IPO a few years back and it now looking to literally save the world and the economy with its mRNA vaccine, Sana is looking for a $150 million IPO for its range of preclinical stem cell and gene control platforms.

That $150 million could, if history repeats itself, swell to be much more than that: It raised a gigantic $700 million last summer from a who’s who of VCs including Arch Venture Partners, Flagship Pioneering, the Canada Pension Plan Investment Board, Baillie Gifford, F-Prime Capital, the Alaska Permanent Fund, the Public Sector Pension Investment Board, Bezos Expeditions, GV, Omega Funds, Altitude Life Science Ventures and “multiple unnamed institutional investors.”

Many other early-stage biotech have also lowballed their IPO target only to see it eventually grow to 50% or 100% more than that.

Last year, Sana licensed technology from Harvard University to further its efforts to develop off-the-shelf cell therapies, its main pipeline focus. The goal is to genetically modify and differentiate stem cells to create cell therapies that are cloaked from the immune system.

Using this, Sana said at the time it plans to harness these resources to create off-the-shelf cell therapies capable of treating a range of diseases. To achieve that goal, Sana will need to find ways to stop the immune system from rejecting the cells as foreign.

The biotech, run by a bunch of former Juno execs, is focused on a series of disease areas including oncology, diabetes, central nervous system disorders, cardiovascular diseases and genetic disorders.

All of its candidates are, however, in preclinical development, with IND submissions for clinical work not expected until 2022 and 2023, according to its Securities and Exchange Commission filing.

“Our vision is to build the pre-eminent company focused on engineered cells to create medicines for patients,” it said in its filing. “Our mission is to do so at a scale that allows broad accessibility for patients so that we can democratize access to curative therapies.

“To achieve this, we have strategically focused on the key limitations for generating engineered cell therapies, whether the cell modulation occurs in vivo or ex vivo. We also continue to aggregate the people and technologies that will allow us to research, develop, manufacture, and ultimately commercialize differentiated products across a range of diseases.”

It plans to list as "SANA" on the Nasdaq.  

https://www.fiercebiotech.com/biotech/secretive-sana-still-a-year-away-from-clinic-files-for-ipo-after-a-mammoth-raise

Liquid Biopsy Predicts Colon Cancer Relapse Months Before CT Test

Detection of circulating tumor DNA (ctDNA) after surgery for colorectal cancer (CRC) identified patients with a high risk of relapse, which could be modified by adjuvant chemotherapy in some cases, data from a prospective study showed.

Among 218 patients with postoperative ctDNA results, 20 had detectable ctDNA, and 15 (75%) subsequently had disease recurrence. The five patients who did not relapse all received adjuvant chemotherapy. By comparison, 198 patients who tested negative for ctDNA had a relapse rate of 13.6%.

In a subgroup of 155 patients with postoperative measurement of ctDNA and carcinoembryonic antigen (CEA), positive ctDNA results had a significant association with relapse-free survival (RFS) whereas CEA did not, reported Tenna V. Henriksen, a PhD candidate at Aarhus University in Denmark, at the Gastrointestinal Cancers Symposium virtual meeting.

"We saw that patients with ctDNA detected immediately after surgery had a very high risk of recurrence," Henriksen said. "We also saw that longitudinal monitoring increased the predictive power of ctDNA. Molecular recurrence by ctDNA was detected a median of 8 months before radiological detection of recurrence. Using longitudinal testing with ctDNA outperforms CEA in recurrence-free survival prediction."

Randomized trials of ctDNA in different clinical settings will be required to move ctDNA into clinical practice, and several studies have already begun, she added.

Despite improvements in curative-intent treatment for stages I-III CRC, 20%-30% of patients relapse. Better detection of minimal residual disease (MRD) could improve postoperative risk assessment, and earlier detection of recurrence would allow more patients to receive curative-intent therapy after recurrence and lead to better survival, said Henriksen. Among potential strategies to detect MRD, ctDNA has produced promising results in several studies.

Investigators organized a clinical study to test the hypothesis that postoperative ctDNA measurement could identify patients with MRD and stratify patients into high- and low-risk groups. Henriksen and colleagues also wanted to assess post-treatment relapse risk in ctDNA-positive patients and determine the lead time from ctDNA detection to radiographic recurrence.

Data analysis included 260 patients with stages I-III CRC, 48 of whom relapsed after curative-intent treatment. The cohort consisted of four patients with stage I disease, 90 with stage II, and 166 with stage III. Henriksen reported that 165 patients received adjuvant therapy, and relapse-free patients had a median follow-up of 29.9 months.

Assessment of ctDNA was performed in 218 patients with the Natera (Signatera) assay, which identified 20 patients with detectable ctDNA (MRD positive) and 198 with no detectable ctDNA. A positive ctDNA test was associated with a recurrence hazard ratio of 11.0 (95% CI 5.9-21, P<0.0001). Among patients who received adjuvant chemotherapy, a positive ctDNA test at the end of treatment was associated with a recurrence rate of 83.3% as compared with 12.5% for those who had negative ctDNA tests (HR 12, 95% CI 4.9-27, P<0.0001).

Longitudinal assessment of ctDNA showed that the risk of recurrence increased over time in ctDNA-positive patients and decreased in ctDNA-negative patients (89.3% vs 3.4%, HR 51, 95% CI 20-125, P<0.0001).

In a subgroup of 29 patients with clinical recurrence detected by CT scan, ctDNA detection occurred a median of 8.1 months earlier, said Henriksen.

Investigators compared the performance of ctDNA with the tumor-associated protein CEA. Measurement of postoperative CEA (n=175) and after adjuvant chemotherapy (n=99) did not have a significant association with the risk of recurrence. Longitudinal assessment of CEA (n=197) did predict an increased risk of recurrence (HR 4.9, 95% CI 3.2-15, P<0.0001) but not as well as longitudinal ctDNA (n=197, HR 95.7, 95% CI 28-322, P<0.0001).

Looking Ahead

Two clinical trials of ctDNA-guided clinical management have already begun, said Henriksen. The IMPROVE-IT study involves patients with stage I or low-risk stage II CRC, a group who usually does not receive adjuvant chemotherapy. Studies have suggested that 10%-15% of such patients are undertreated. In the trial, ctDNA-positive patients will receive adjuvant chemotherapy, and ctDNA-negative patients will receive no adjuvant therapy but will be followed with serial ctDNA testing.

IMPROVE-IT2 compares ctDNA and radiologic surveillance for recurrence. Currently, only 20% of patients with radiologically detected relapse are eligible for curative-intent therapy. In the clinical trial, patients with ctDNA-positive tests will undergo intensified radiologic surveillance and intensified treatment, whereas those with negative ctDNA tests will be followed with serial ctDNA testing only.

The study reported by Henriksen adds to a growing body of evidence for the "convincing prognostic ability of circulating tumor DNA following surgical resection," said invited discussant Michael Overman, MD, of the MD Anderson Cancer Center in Houston. However, the assay used in the study is one of multiple approaches to ctDNA detection under investigation.

"The key for us is to understand how to use circulating tumor DNA to guide therapy," he said. "It must be recognized that the availability of a test is not the same as the actionability. To answer this question, I encourage all of us to support the enrollment of ongoing randomized clinical trials using circulating tumor DNA to help optimize our use of adjuvant therapy for colorectal cancer patients."

Disclosures

The study was supported by the Danish Council for Independent Research, the Novo Nordisk Foundation, the Danish Cancer Society, and Natera. Some co-authors are Natera employees.

Henriksen disclosed no relevant relationships with industry. Co-authors disclosed relevant relationships with Natera, Mission Bio, Bayer, Pierre Fabre, Merck Serono, Roche, Servier, AbbVie, Amcure, Array BioPharma, Astellas, AstraZeneca, BeiGene, Bristol-Myers Squibb, FibroGen, Genentech, Johnson & Johnson, Lilly, MedImmune, Merck, Novartis, Sierra Oncology, Takeda, Tesaro, and Theradex.

Primary Source

Gastrointestinal Cancers Symposium

Source Reference: Henriksen TV, et al "Circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, and early relapse detection after treatment in colorectal cancer patients" GICS 2021.

https://www.medpagetoday.com/meetingcoverage/mgics/90745

Cambridge U develops DNA test for COVID-19 secondary, hospital-acquired infections

 Researchers at the University of Cambridge have developed a DNA test to help spot dangerous secondary infections that may develop during COVID-19 treatment—such as cases of pneumonia associated with ventilator equipment provided during intensive care.

Patients under mechanical ventilation are typically given anti-inflammatory drugs to ease damage to their lungs, however this may leave them more susceptible to bacteria and fungi in the hospital.

The test, developed at Cambridge University Hospitals in collaboration with Public Health England, is designed to identify the infection and help suggest the appropriate course of antibiotics. 

The approach—which promises to be much faster than culturing bacterial samples in a lab, taking about four hours total to pick up 52 different pathogens—is currently being rolled out to healthcare providers under the university’s NHS Foundation Trust.

"Early on in the pandemic we noticed that COVID-19 patients appeared to be particularly at risk of developing secondary pneumonia, and started using a rapid diagnostic test that we had developed for just such a situation," said Andrew Conway Morris, of Cambridge's Department of Medicine, who co-authored a paper examining the rates of ventilator-associated pneumonia among COVID-19 patients.

"Using this test, we found that patients with COVID-19 were twice as likely to develop secondary pneumonia as other patients in the same intensive care unit," Morris said. As to the reason why, people with severe infections tend to spend more time on ventilators, and may also have poorly regulated or overactive immune system in the face of the virus.

It also marks one of the first times that high-throughput PCR sequencing has been employed in the university’s routine clinical practice in such a manner.

"We found that although patients with COVID-19 were more likely to develop secondary pneumonia, the bacteria that caused these infections were similar to those in ICU patients without COVID-19," said Cambridge researcher and lead study author Mailis Maes. "This means that standard antibiotic protocols can be applied to COVID-19 patients."

https://www.fiercebiotech.com/medtech/cambridge-univ-researchers-develop-dna-test-for-covid-19-s-secondary-hospital-acquired

Indian companies prepare to buy vaccines for employees

 

Several Indian companies are making plans to buy COVID-19 vaccines for their employees, just days after the country's government began one of the world's largest vaccination drives with healthcare and other frontline workers.

Steel producer Jindal Steel and Power Ltd, autos-to technology conglomerate Mahindra Group and consumer goods giant ITC Ltd have begun initial checks on hopes that vaccines will be available for purchase after the government covers priority segments.

"ITC would certainly like to extend the vaccination to employees... We have approached vaccine manufactures and are in exploratory talks," Amitav Mukherji, head of corporate human resources, said.

India is currently using Britain's Oxford University/AstraZeneca vaccine, which is being produced in India by the Serum Institute, and a government-backed alternative developed by India's Bharat Biotech.

Tata Steel said it would get employees inoculated as soon as shots are available commercially.

Indian factories are recovering from one of the world's strictest lockdown last year, which led to large-scale job losses and migration of workers back to their villages.

"We are reaching out to vaccine manufacturers for bulk supply of doses and will try to get these doses after completion of all frontline Covid warriors' vaccination," Pankaj Lochan, chief human resource officer, JSPL, said.

The company did not give more details on either the number of doses it plans to buy or with whom it was in talks with.

The world's second-most populous country, India trails only the United States in numbers of COVID-19 infections.

Billionaire Anand Mahindra-led Mahindra Group said it was also interested in buying vaccines for employees "in accordance with the priorities and sequence to be specified by the government".

Global consumer goods giant Unilever last week said it was strongly encouraging employees to get vaccinated as soon as possible and floated the idea that it could buy shots to share with people in poorer countries.

As governments rush to inoculate the most vulnerable, however, most corporations globally have so far been quiet on whether they would seek to secure early supplies for employees.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/Indian-companies-prepare-to-buy-vaccines-for-employees-32218471/

Grifols begins trial of treatment for immediate Covid immunity

 

• The treatment could be administered in primary care centers to people who test positive for COVID-19, avoiding hospitalization due to the progression of the disease and complementing the vaccine in the early phase after vaccination
• The medicine, an anti-SARS-CoV-2 immunoglobulin, given subcutaneously, would provide immediate protection after exposure to the virus and could be used to protect the elderly and healthcare workers. It could also be given to immunocompromised patients for whom the vaccination isn't indicated
• The treatment is based on the Grifols immunoglobulin Gamunex®-C, and contains anti-SARS-COV-2 polyclonal antibodies from plasma donors who have recovered from COVID-19
• The clinical trial to evaluate the safety and efficacy of the plasma-derived medicine will have doctors Oriol Mitjà and Bonaventura Clotet as the principal researchers and is expected to begin in early 2021

Grifols (MCE: GRF, MCE: GRF.P, NASDAQ: GRFS), a global leader in the development of therapies with plasma-derived proteins with a track record of more than 100 years dedicated to enhancing people's health and well-being, today announced it will begin a clinical trial in Spain to evaluate the safety and efficacy of a new COVID-19 drug based on the Grifols immunoglobulin Gamunex®-C and containing anti-SARS-CoV-2 polyclonal antibodies from plasma donors who have recovered from the disease.

The new drug would provide immediate post-exposure protection against the virus and would be especially useful as a complement to the vaccine in the early phase after vaccination. In addition, it could protect the elderly and healthcare workers as well as immunocompromised patients for whom vaccination isn't recommended. It could also help contain outbreaks in places where the vaccination hasn't begun or is still underway.

Grifols expects this clinical trial, led by the researchers Oriol Mitjà and Bonaventura Clotet, from Germans Trias i Pujol Hospital in Barcelona, to begin in February 2021, with the possibility of results in the spring.

About 800 patients, all asymptomatic but having tested positive for the virus in a diagnostic test, will participate in the clinical study, receiving subcutaneously Grifols' immunoglobulin rich with anti-SARS-CoV-2 antibodies.

The Grifols immunoglobulin Gamunex®-C, whether administered intravenously, intramuscularly or subcutaneously, has proven to be safe and efficacious in the prevention of diverse infectious diseases in immunocompromised patients and has been used for this for more than 15 years.

https://www.biospace.com/article/releases/grifols-begins-clinical-trial-of-a-new-treatment-that-would-provide-immediate-immunity-against-covid-19/

Quest Diagnostics Wins CDC Contract to Sequence COVID-19 Gene Variants

  Quest Diagnostics (NYSE: DGX), the world's leading provider of diagnostic information services, today announced that it has entered into an agreement with the Centers for Disease Control and Prevention (CDC) to provide genomic sequencing to identify new mutations in, and patterns of transmission of SARS-CoV-2, the virus that causes COVID-19. Financial terms of the agreement are not disclosed.

The goal of the collaboration is to aid the CDC in conducting a large-scale longitudinal genomic survey of the SARS-CoV-2 virus using a random set of samples collected from Quest's labs across the United States. The company will perform the sequencing from its advanced diagnostics laboratory in San Juan Capistrano, Calif.

Viruses can mutate over time. In recent weeks, highly transmissible variants of the SARS-CoV-2 virus first discovered in the United Kingdom and South Africa have been identified in the United States.  

Quest Diagnostics will sequence the viral genomes of random de-identified samples that test positive in the course of providing molecular diagnostic testing for SARS-CoV-2 for providers and patients, and provide the CDC with completed whole viral sequences. These data will be combined with the results of other data provided to the CDC by national, state, academic, and commercial labs to help meet the CDC survey's aims.

https://www.prnewswire.com/news-releases/quest-diagnostics-granted-cdc-contract-to-sequence-covid-19-gene-variants-to-aid-public-health-response-to-covid-19-301209723.html

Celltrion closes in on COVID-19 antibody market after trial success

 South Korea’s Celltrion has announced encouraging top-line results for its potential antibody therapy for COVID-19, with the first part of a phase 2/3 trial showing it could cut recovery times and chances of progression from moderate to more severe disease.

Several other companies are also working on antibody therapies and Eli Lilly’s bamlanivimab gained an FDA Emergency Use Authorization in November last year, shortly after Regeneron’s cocktail of casirivimab and imdevimab.

There are doubts over efficacy of Lilly’s antibody, which failed to produce benefits in hospitalised patients in a phase 3 trial last month.

AstraZeneca is developing an antibody therapy and so is its UK rival GlaxoSmithKline, which this week announced a deal with VIR Biotechnology to trial VIR-7832 in mild to moderate COVID-19 patients.

Until COVID-19 hit Celltrion was best known for producing biosimilars, which are near-copies of biologic drugs that have been shown to be as safe and effective in rigorous trials and tests.

But the company is using its expertise to develop an antibody therapy, CT-P59, to help the effort against the pandemic.

Celltrion filed the therapy with the Korean regulator at the end of December and plans to submit data to regulators in Europe and the US in the coming months.

A spokesperson said in an email that company is “working closely with the regulatory agencies to accelerate the regulatory procedures”.

Part I of the trial enrolled 327 patients with mild-to-moderate symptoms of COVID-19 across three treatment groups (40mg/kg, 80mg/kg and placebo), in which approximately 60% of patients with moderate symptoms suffered from COVID-19 related pneumonia.

This data analysis has demonstrated that at day 28, CT-P59 treated patients presented with a significantly reduced risk of COVID-19 related hospitalisation and oxygenation without mortality.

When compared to placebo, CT-P59 treated patients reported reduced progression rates to severe COVID-19 by 54% for mild-to-moderate patients and 68% for moderate patients aged 50 years and over.

CT-P59 treatment groups also reported with significantly shortened time to clinical recovery ranging from 3.4 to 6.4 days quicker compared to placebo.

Patients treated with CT-P59 recovered 3.4 days earlier than those in a placebo group, while patients with pneumonia reported that their recovery time was 5.1 days shorter compared with placebo.

A group of patients with moderate disease aged 50 years and over treated with CR-P59 reported that their recovery time was 6.4 days shorter than placebo, the company said.

CT-P59 treated patients rapidly and significantly reduced viral load through Day 7 compared to placebo. Top-line results from the trial shows CT-P59 to have a positive safety profile, comparable to that of the placebo group, with no serious adverse advents reported.

Infusion related reactions were mild and transient, with the CT-P59 treatment group having reported 0.5%, compared to 1.8% reported with placebo.

https://pharmaphorum.com/news/celltrion-closes-in-on-covid-19-antibody-market-after-trial-success/