Regulus: Positive Topline Data in Phase 1 Trial of RGLS8429 for Polycystic Kidney Disease

 Phase 1b Multiple Ascending Dose (MAD) Study Initiated

RGLS8429 in healthy volunteers was well-tolerated with dose-proportional PK

Topline data from first cohort of patients with ADPKD anticipated in 1H 2023

Regulus Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs (the "Company" or "Regulus"), today announced positive topline safety and PK data from its Phase 1 SAD clinical trial of RGLS8429. Additionally, the Company announced the initiation of its Phase 1b MAD clinical trial of RGLS8429.

https://finance.yahoo.com/news/regulus-therapeutics-announces-positive-topline-120000486.html

Regeneron Data on Squamous Cell Carcinoma Presented at ESMO, Published in NEJM

 63% combined pathologic response rate for neoadjuvant Libtayo monotherapy in stage II to IV resectable CSCC per primary analysis of a confirmatory Phase 2 trial

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive clinical data for an investigational regimen of PD-1 inhibitor Libtayo^® (cemiplimab) as neoadjuvant monotherapy in stage II to IV resectable cutaneous squamous cell carcinoma (CSCC). The data, from the primary analysis of a confirmatory Phase 2 trial, were presented in an oral session at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris and concurrently published in the New England Journal of Medicine (NEJM).

https://www.biospace.com/article/releases/positive-neoadjuvant-libtayo-cemiplimab-monotherapy-data-in-resectable-cutaneous-squamous-cell-carcinoma-presented-at-esmo-and-published-in-nejm/

Mersana: FDA Fast Tracks Treatment for Triple-Negative Breast Cancer

 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to XMT-1660 for the treatment of adult patients with advanced or metastatic triple-negative breast cancer (TNBC). XMT-1660 is a B7-H4-directed Dolasynthen antibody drug conjugate with a precise, target-optimized drug-to-antibody ratio (DAR 6) and Mersana’s clinically validated DolaLock microtubule inhibitor payload with controlled bystander effect.

https://finance.yahoo.com/news/mersana-therapeutics-announces-fda-fast-120000821.html

Japan OKs Partial Change to Authorization for Moderna Omicron-Targeting Bivalent Booster COVID Vax

 Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced that it has received approval from the Ministry of Health, Labour and Welfare (MHLW) in Japan for a partial change to a new drug application for its Omicron-targeting bivalent COVID-19 booster, mRNA-1273.214 (Spikevax Bivalent Original/Omicron BA.1). Spikevax Bivalent Original/Omicron contains mRNA-1273 (Spikevax) and a vaccine candidate targeting the Omicron variant BA.1.

"COVID-19 continues to threaten public health in Japan, as infections by Omicron and its subvariants continue. mRNA-1273.214 has demonstrated the ability to trigger significantly higher antibody titers against Omicron BA.1 and BA.4/5 subvariants when compared with mRNA-1273," said Rami Suzuki, President & Representative Director of Moderna Japan. "We will continue to work with the Ministry of Health, Labour and Welfare to bring this important vaccine to people in Japan as soon as possible to help protect against COVID-19."

The approval from the MHLW is based on clinical trial data from a Phase 2/3 trial, in which mRNA-1273.214 met all primary endpoints, including superior neutralizing antibody response against Omicron (BA.1) when compared to the currently authorized 50 µg booster dose of Spikevax (mRNA-1273) in previously uninfected participants. A booster dose of Spikevax Bivalent Original/Omicron (mRNA-1273.214) increased neutralizing geometric mean titers (GMT) against Omicron approximately 8-fold above baseline levels. In addition, Spikevax Bivalent Original/Omicron (mRNA-1273.214) elicited higher neutralizing antibody titers against the Omicron subvariants BA.4 and BA.5 when compared to Spikevax (mRNA-1273) regardless of prior infection status or age, including in those aged 65 and older. mRNA-1273.214 was generally well tolerated, with a reactogenicity and safety profile consistent with the currently authorized booster.

Moderna has received authorization decisions for Omicron-targeting bivalent boosters in the United States, Australia, Canada, Europe, Switzerland, South Korea, Taiwan, and the UK to date and has completed regulatory submissions worldwide. In Japan, Takeda Pharmaceutical Co. Ltd. continues to provide distribution support for Spikevax Bivalent Original/Omicron under the current national vaccination campaign for Moderna's COVID-19 vaccines for a transitional period. Supply is expected to commence during September.

Authorized Use

Spikevax bivalent Original/Omicron is indicated as a booster dose for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older. One 0.5 mL dose is provided intramuscularly.

https://finance.yahoo.com/news/ministry-health-labour-welfare-japan-110000701.html

Alphabet’s Verily raises $1 billion as tech giants enter red hot healthcare sector

 Verily, the life sciences business under Alphabet, said Friday that it has raised $1 billion, capital that will be used to expand its data-driven healthcare products tailored to individuals.

The round was led by Alphabet, the company said in its announcement.

Verily also announced changes to its executive team that will go into effect January 2023. The company’s founder Andy Conrad will become executive chairman of the Verily board. Stephen Gillett, who is president of the company, will be promoted to CEO. Gillett initially joined Verily as an operational advisor and to lead the company’s cybersecurity efforts. At the time, he was co-founder and CEO of Chronicle, an Alphabet cybersecurity company that is now part of Google Cloud.

Deepak Ahuja is leaving the CFO spot by the end of the month. Ahuja, the former and first CFO at Tesla, has been hired as the first chief financial and business officer at drone delivery and logistics startup Zipline. Ahuja will remain an advisor, the company said, adding that a search for a new CFO will begin immediately.

The influx of capital and executive shuffling come as Verily readies itself for a new phase of growth in a red hot healthcare sector that has attracted tech giants like Amazon and Apple. Earlier this year, Amazon acquired One Medical, a primary care provider that leverages in-person, digital and virtual interactions in its services, in a deal valued at $3.9 billion.

Verily is particularly interested in “precision health,” a term meant to describe combining research, clinical and non-clinical data and computing power to provide healthcare customized to a person’s specific needs. In other words, Verily — which was born out of Google X in 2015 — aims to use technology to provide medical care for individuals instead of everyone.

Verily said the funds may also be used to invest in strategic partnerships, global business development and potential acquisitions. The company has already landed a several partnerships and completed at least one acquisition. In 2021, the company bought research software developer SignalPath to expand its clinical trial system. It also has partnered with Lumea, L’Oreal, the Mayo Clinic and Microsoft.

https://techcrunch.com/2022/09/09/alphabets-verily-raises-1-billion-as-tech-giants-enter-red-hot-healthcare-sector/

'How to reduce youth violence'

 There’s a new violent tragedy seemingly every day in our communities, whether a mass murder in Sacramento, a school shooting in Highland Park or Uvalde, or a suicidal death of despair. Our children and young adults are struggling.

A tragedy within this tragedy is that we know how to prevent children from growing up to be violent, but we haven’t done enough about it. A Secret Service study found almost two-thirds of school shooters had problems getting along with peers — including being bullied — in the period prior to the shooting. The National Institutes of Health (NIH) has invested heavily in research over the past 30 years and researchers now know a great deal. 

Our research group has learned that efforts to support children, families and schools can change children’s paths from school failure, early drug use and delinquency to a positive outcome. One program is Fast Track, an NIH-funded project that started in 1990 in four U.S. communities. Scientists worked with high-risk first-grade children to develop the skills, knowledge and attitudes to have healthy relationships with others and make smart decisions when faced with life’s challenges. The research revealed that children assigned to Fast Track grew up to spend less time in prison, have fewer problems of substance abuse and are less of a financial burden to society. Fast Track is just one example of carefully tested evidence-based programs to reduce violent and mental disorder as well as promote healthy functioning in children and youth. The Blueprints Program is other exemplar programs.

The development of social competence is like the development of literacy: It is not simply a matter of free will, but a lifelong process that involves learning specific component skills and attitudes accompanied by a love for social connectedness. As with literacy, we know the required skills: emotion understanding, self-control, social problem solving, self-awareness, executive function, delay of gratification and more. As with literacy, we know that a love for social connectedness begins at birth through caring interactions with parents and other caregivers and continues through interactions with peers and structured group experiences in school. As with literacy, this path can be tragically interrupted by abusive trauma or failure experiences.

We now have ways to build social competence in our children. The path to a peaceful and fulfilling social life begins at birth through a secure parent-infant bond, and we have resources to support this relationship. We now have peer coaching programs to help kids develop strong peer relationships. We know social competence gets legs with structured, social-emotional learning programs offered in elementary school and is buttressed by more intensive social skills training for those who need extra support. 

We need a coordinated, all-out effort to eliminate disparities in outcomes across race and income groups. We would not stand by idly until a child becomes 18 and then throw that child in prison because he or she cannot read. Instead, we have created universal public schools, classroom curricula enhanced by targeted special education programs, as well as a culture of literacy development that begins at birth with books in the home, computer-assisted skills learning and more. But with social competence, we do very little, and then, indeed, we will throw an 18-year-old child in prison for acting incompetently. 

Broad use of these programs to support children should be one part of a larger strategy that includes eliminating structural inequities, poor quality housing and other community resource limits experienced by many children and families. To make healthier communities, we need both effective programs for individual children and structural changes that reduce inequities. 

We propose an approach that supports children’s mental health and well-being from birth onward that focuses on the important aspects of a child’s life. The approach must help parents connect with their child in the first years of life. It must support high-quality universal early childcare and education experiences. It must re-craft schooling to incorporate social-emotional learning curricula and peer connections as central goals. It must include regular screening across the lifespan to identify those in greater need so that targeted interventions can support children. It must be integrated with traditional education to create synergies between learning to read and learning to get along. Engineering such a comprehensive approach requires collaboration across health and education sectors. The ball could get rolling through leadership from the executive branch and governors.

Maybe, just maybe, a coordinated all-out effort to make the next generation of children socially competent could prevent violent tragedies like those we see today and promote a generation of healthy, productive and engaged citizens.

Mark Greenberg is the founding director of the Edna Bennett Pierce Prevention Research Center and is emeritus professor at Penn State.

Kenneth Dodge is the William McDougall distinguished professor of public policy and professor of psychology and neuroscience at Duke University.

They are researchers representing the Conduct Problems Prevention Research Group.

https://thehill.com/opinion/education/3637979-how-to-reduce-youth-violence/

Moderna’s Second Act: Seeking Success after COVID-19

 Moderna catapulted into public consciousness after developing an effective COVID-19 vaccine in less than a year. Now that most people in North America and Europe are vaccinated and the pandemic is diminishing, the company is looking for its second act.

An ambitious plan is well underway to ensure Moderna continues to thrive. Not surprisingly, it is piggybacking off its recent success in mRNA vaccines with nearly four dozen programs in development.

“That’s one of the beauties of the mRNA technology – it has a lot of applications,” said Margery Fischbein, managing director of the healthcare practice at investment bank Cassel Salpeter & Co., in an interview with BioSpace. “Therefore, the portfolio is not as diverse as the numbers would suggest.”

This is because several programs are combinations (such as flu and SARS-CoV-2, or multiple SARS-CoV-2 variants) and vaccines for individual viral mutations. 

But, this can be incredibly efficient. Melissa J. Moore, Ph.D., CSO, scientific affairs at Moderna, elaborated on the technology's utility.

“While each mRNA medicine provides a unique instruction set based on the nucleotide sequence in the mRNA, the manufacturing processes and means of mRNA delivery are the same across many different medicines,” she told BioSpace. “Thus, we can create new medicines just by changing the sequence of nucleotides in the mRNA.” 

The Pipeline

Of more than 40 vaccines and therapeutics in development at Moderrna, about a dozen are geared to COVID-19. Phase III candidates include three COVID-19 vaccines for wildtype SARS-CoV-2 and the Omicron variant, as well as vaccines for flu, respiratory syncytial virus and cytomegalovirus.

In Phase II, Moderna is advancing vaccines for cancer and Zika virus, as well as five COVID-19 vaccines for combinations of wildtype, Beta and Delta variants. It’s also developing a next-generation COVID-19 vaccine that can be stored between 2 and 5°C. This would be a significant improvement over the deep-frozen temperature requirements of the initial vaccine.

At the earlier stages, 17 programs are in Phase I development. They include vaccines for HIV, cancer, Nipah, flu, RSV, COVID-19 and three systemic intracellular therapies. Preclinical programs include 13 vaccines for a wide range of applications, including Epstein Barr, flu and COVID-19 and therapeutics for cystic fibrosis and Crigler Najjar syndrome.

The ability to build vaccines using the existing mRNA platform “provides a huge advantage compared to traditional medicines, as we don’t have to reoptimize every parameter (e.g., the PK/PD properties and toxicology profile) for every new medicine,” Moore pointed out.

Another advantage is that Moderna does not need dedicated manufacturing equipment for each vaccine or therapeutic. “One mRNA medicine manufacturing facility can make many different vaccines and therapeutics simply by changing the mRNA sequence,” she explained. 

All of these programs, however, are in development. This is, by definition, aspirational. Currently, Moderna is accruing orders, approvals and authorizations for its existing products.

The U.S. government recently agreed to purchase another 66 million doses of Moderna’s bivalent booster containing Omicron and wild-type SARS-CoV-2. The Canadian government purchased another 4.5 million doses of that bivalent booster in late August. The U.K.’s Medicines and Healthcare Products Regulatory Agency recently authorized that bivalent booster and the EMA Committee for medicinal products for human use recommended its use in adolescents in the EU.

Financial Ups and Downs

Moderna’s unaudited financial results for the first half of 2022 show sales of $10.5 billion, and approximately $18.1 billion in cash and investments. The company has bought back 18 million shares of stock so far - 9 million of which were bought in Q2 for $1.3 billion. Recently, it announced an open-ended plan to buy back another $3 billion worth of its stock. 

“This is something companies often do when they have excess cash and are profitable,” Fischbein said.

Moderna’s second quarter financial results showed year-over-year growth in product sales of 8%, grant revenue of 32% and collaboration revenue of 94% (due to a project with AstraZeneca). This resulted in a 9% year-over-year increase in revenue.

At the same time, however, the cost of sales increased 84%, R&D costs were up 69% and total operating expenses were 78% greater than in the same quarter of 2021. Overall, net income declined 21%, compared to Q2 2021. Moderna reported Q2 earnings per share were $5.24, which exceeded analysts’ expectations but were still less than the same quarter last year.

Moderna has $21 billion worth of signed, advance purchase agreements but despite strong sales, share prices are down from their high of approximately $430 in October 2020 to around $142 at close of business Friday.

Watching the decline, analysts have generally lowered their target prices for the stock, with a consensus target price of $227.75, according to MarketBeat. Despite authorizations for Moderna’s COVID-19 booster shots in children in the U.S., Canada and Australia, and adolescents in the EU, analysts predict sales to fall throughout 2023 and 2024 before rebounding, according to Investors.com. 

Rapid Growth

Moderna has grown from 760 employees in 2018 to more than 3,000 today – quadrupling in only four years. When any company grows so quickly, maintaining the company culture is challenging, Fischbein said. “A major area where they’ve grown has been in manufacturing, which tends to be both capital- and employee-intensive.”

With that comes the challenge of keeping everyone mission-focused, Ira Z. Leiderman, managing director of the healthcare practice at Cassel Salpeter & Co., added.

“It’s hiring senior level people a notch below the C-suite who can manage their departments and programs and do their best to get a return on investment,” he told BioSpace. “Keeping everyone rowing in the same direction is a challenge for any young company.”

Richard Brandenstein, founding partner at FBR Law, said, “A huge mistake businesses make during periods of rapid growth is not imbursing employees. Your workforce will realize you are growing and high performers who don’t feel they are treated equally may leave.”

Looking Forward

Already, “Moderna’s platform has been proven safe and efficacious, and it has developed a good rapport with regulators at the FDA and EMA, which is a testament to their clinical affairs staff as well as their ability to execute fairly large clinical studies very effectively and efficiently,” Leiderman said.

Whether Moderna can sustain its current level of success is unknown. “This is biotech,” he said, which often encounters surprises even in late-stage clinical trials. “The good thing is that the company has the resources it needs,” to afford some misses and support some successes.

 In the coming decades, Moore said she envisions Moderna as a “leader in mRNA medicines, with a broad portfolio of vaccines and therapeutics,” with rapid development and manufacturing capabilities. There’s a more than fair chance she’s right.

https://www.biospace.com/article/moderna-s-second-act-seeking-success-after-covid-19/