Pfizer Alleges Stolen Trade Secrets at Heart of Regor Therapeutics Launch

 A $1.5 billion diabetes partnership between Eli Lilly and China-based Regor Therapeutics Group is at the center of a lawsuit filed by Pfizer, claiming that the founders of Regor are using company trade secrets to develop their therapeutics at the center of the partnership with Eli Lilly.

In a lawsuit filed in federal court this week, Pfizer alleged that its former employees Xiayang Qiu and Ming Zhong, now executives at Regor, which has offices in Boston, misappropriated confidential data surrounding an anti-obesity and diabetes drug in development at Pfizer to launch Regor. In its filing, Pfizer said that forensic analysis “confirmed” the two had misappropriated the information. Bloomberg Law reported Pfizer analyzed the May 2020 publication of a 2019 Regor patent application. Following the discovery of the patent, Pfizer launched an internal investigation, which quickly zeroed in on Qui and Zhong.

Pfizer discovered that the mobile phone Zhong returned to Pfizer was not his company-issued phone. The Pfizer phone has not been recovered. In its complaints, Pfizer said computer forensics revealed that Zhong had downloaded confidential documents to his laptop and deleted several crucial files.

According to the lawsuit, Qiu worked at Pfizer to focus on the discovery of therapeutic compounds and how they could interact with proteins within the body. As a director of clinical outsourcing, Zhong worked with third-party research vendors. Their work intersected on an analysis of how a key receptor “interacted with certain compounds to aid research into the diabetes-and-obesity treatment,” Bloomberg reported.

In the complaint, Pfizer said the two employees began expressing dissatisfaction about working at the pharma giant in 2017. They started to send emails back and forth about establishing their own company. During a 2018 trip to China, Qui secured financial backing from investors. Bloomberg reported that Pfizer accused Qui and Zhong of stealing confidential documents related to their work and research into other potential drugs. 

Pfizer argued that Zhong and Qui developed a presentation around the misappropriated data, which helped Regor leap out of the gate since its founding, raise $90 million in a Series B financing round, score the partnership with Eli Lilly and enter the clinic with an oncology asset.

“Without the critical head start Zhong and Qiu’s theft provided, Defendants could not have ‘developed’ their own purported treatment in such a short amount of time,” the complaint said, according to additional reporting by Reuters.

In an email to BiopSpace late Thursday, a Regor spokesperson said the company is aware of the lawsuit but believes it is meritless and intends to vigorously defend itself against the allegations. 

In December, Eli Lilly announced the upfront payment of $50 million to Regor, which partially included an equity investment into the China-based company. The terms also allow Regor to receive up to $1.5 billion in potential payments based on clinical and commercial milestones for developing therapeutics related to common metabolic disorders that include diabetes, obesity and nonalcoholic steatohepatitis. Lilly is expected to take the lead on the project by harnessing Regor’s CARD (Computer Accelerated Rational Discovery) platform to accelerate the development of any assets.

In an email to BioSpace, Eli Lilly said the company does not have any public comments on the lawsuit and its potential ramifications for the partnership with Regor at this time. 

https://www.biospace.com/article/pfizer-claims-former-researchers-stole-secrets-related-to-metabolic-disease-research-at-center-of-an-eli-lilly-partnership-struck-in-december/

Three COVID-19 exposures needed for broad immunity

 The immune system develops a high-quality antibody response after three encounters with the coronavirus spike protein. These antibodies are also capable of neutralizing omicron efficiently. This applies to people who are triple-vaccinated, to those having recovered and then received two vaccinations and to double-vaccinated individuals who have experienced a breakthrough infection. These are results of a study which tracked the antibodies of vaccinated and recovered individuals for two years.

Since the beginning of the COVID-19 pandemic, SARS-CoV-2 has continued to evolve, with new variants of concern (VoCs) spreading rapidly. Highly contagious and partially capable of evading the immune response, omicron has become the dominant variant in most countries.

Answers to the question how the immune systems can be "educated" to battle omicron and other immune escape variants of the virus are provided by a team led by Prof. Ulrike Protzer, Director of the Institute of Virology at the Technical University of Munich (TUM) and Helmholtz Munich, Percy Knolle, Professor of Molecular Immunology at TUM, and Prof. Oliver T. Keppler (Max von Pettenkofer Institute and Gene Center Munich at LMU). As they report in Nature Medicine, a total of three exposures to the viral spike protein leads to production of virus neutralizing antibodies not only in high quantity, but also high quality. These high-quality antibodies bind to the viral spike protein more vigorously and are also capable of effectively fighting the omicron variant. This applies to triple-vaccinated people, to people who have recovered from COVID-19 and then had two vaccinations, and to double-vaccinated people who then had a breakthrough infection.

Since the beginning of the pandemic, voluntary participants from the staff at TUM's university hospital Klinikum rechts der Isar at risk of infection participated in the study and were regularly tested. The researchers identified individuals who had contracted SARS-CoV-2 during the first wave of the pandemic in spring 2020, and compared them to a second group of people who had not been infected. Subsequently, both groups were offered vaccination with the mRNA-based COVID-19 vaccine from BioNTech/Pfizer and were monitored for almost two years. The cohort comprised 98 recovered persons and 73 persons without prior infection.

"This longitudinal study is particularly exciting, because we can follow how the immune response evolves over time against the virus and after vaccination" says Prof. Knolle, pointing to a study by the team, which has just appeared in Nature Communications. In the new study the team now defined several parameters in the blood of study participants: the concentration of antibodies to the viral spike protein, the binding strength of these antibodies, and their ability to neutralize infection of SARS-CoV-2 variants in cell culture. For estimating the extent of protective immunity, the latter two parameters are particularly important. The study revealed that the ability of the immune system to neutralize the virus correlates only weakly with the antibody titer. Rather, it was critical how effectively these antibodies bind to the virus and thus disable infection.

As predicted from its many mutations, omicron exhibited the most pronounced evasion from neutralizing antibodies compared to all other viral variants tested. "For omicron, you need considerably more and better antibodies to prevent infection" points out Prof. Keppler. The researchers developed a new virus neutralization test, which allowed them to analyze antibodies in many serum samples and different variants of the virus at high throughput rates. Prof. Protzer adds: "A new finding of our study is that people require three separate exposures to the spike protein to build up high-level neutralizing activity against all viral variants, including omicron."

As the scientists report, various constellations are possible for these three spike encounters. Triple-vaccinated people without prior SARS-CoV-2 infection had almost the same titer and quality of neutralizing antibodies against omicron as vaccinated convalescents or people who had a breakthrough infection with delta or omicron. Prof. Keppler: "In all cases, the neutralization activity reached similarly high levels and this was paralleled by an increased binding strength of the antibodies." Prof. Protzer and Prof. Knolle agree: "The immunity built up or strengthened by means of vaccination is key to effective protection against future variants of the virus. A recent breakthrough infection—as irritating and undesirable as it is—has in fact the same effect as an additional vaccination on this important arm of the immune system."

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Persistent T cell response to omicron after infection and vaccination

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More information: Paul R. Wratil et al, Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern, Nature Medicine (2022). DOI: 10.1038/s41591-022-01715-4

Nina Koerber et al, Dynamics of spike-and nucleocapsid specific immunity during long-term follow-up and vaccination of SARS-CoV-2 convalescents, Nature Communications (2022). DOI: 10.1038/s41467-021-27649-y

https://medicalxpress.com/news/2022-02-covid-exposures-broad-immunity.html

BD doubles COVID sales forecast for 2022 even as steep testing dropoff leads to revenue loss

 Nearly two full years into the pandemic, COVID-19 still has the power to make or break a company’s bottom line.

In BD’s case, even though the medtech giant spent the last year introducing new devices and diagnostics and making acquisitions to break into new businesses, it still reported a drop in revenue for the first quarter of its 2022 fiscal year, attributed almost solely to a sharp dip in COVID-related earnings.

BD raked in just under $5 billion for the three-month period ending Dec. 31. That marks a 6% decline compared to the first fiscal quarter of the previous year, when it took in $5.3 billion.

Subtracting the impact of COVID-only diagnostic testing from those totals, however, tells a completely different story. Without those test sales, BD earned $4.8 billion for the quarter, which represents an increase of 8.1% over the previous year’s $4.5 billion COVID-less haul.

That stark difference comes from the fact that BD’s COVID testing revenues for the period amounted to less than a quarter of what it earned in the last three months of 2020—as the coronavirus case count was surging steadily upwards and before vaccines were widely available.

At that time, following the first quarter of its fiscal year 2021, BD reported a massive $866 million take from COVID test-related sales alone. A year later, that number had dropped to $185 million.

Still, the drop in testing revenues—and its mighty effect on quarterly earnings—wasn’t unexpected. In fact, BD’s first-quarter COVID revenues actually outstripped its own forecasts, prompting the company to up its outlook for the full year.

Because that $185 million quarterly total almost met the previous full-year forecast of $200 million in COVID-related earnings, BD has more than doubled its prediction, now expecting to take in about $450 million in the segment throughout its fiscal year 2022. That, in turn, sends its overall revenue forecast up, with BD now predicting a full-year total between $19.55 billion and $19.75, compared to initial expectations that it would fall closer to the $19.3 billion to $19.5 billion range.

To maintain that growth, CEO Tom Polen said in a statement that BD would continue ramping up innovation across its three core segments—medical, life sciences and interventional—and further build out those businesses with more tuck-in acquisitions.

It’s already off to a solid start in the latter category. During the first quarter of its fiscal year, it announced the acquisitions of Scanwell Health, Venclose and Tissuemed, and just this week, it added cancer blood test maker Cytognos to the lineup.

It’s also busy finalizing the spinoff of its diabetes business into a standalone public company, to be named Embecta. With this week’s sign-off from BD’s board of directors, the separation is slated to occur April 1.

Embecta will be led by Devdatt Kurdikar, currently the worldwide president of BD’s diabetes division. That division alone was responsible for about $1.2 billion in revenue for all of fiscal year 2021, which BD is hoping will give Embecta the head start it needs to take the diabetes market by storm.

https://www.fiercebiotech.com/medtech/bd-doubles-covid-sales-forecast-for-2022-even-as-steep-testing-dropoff-leads-to-revenue

Arrowhead ‘changing horses’ for ENaC pulmonary program as phase 1/2 asset shelved

 Arrowhead Pharmaceuticals is ditching a pulmonary drug after it failed to hit the mark in a phase 1/2 trial last year. But the biotech is filling up its quiver with at least two more prospects in the program as a replacemen

Executives reported the pipeline changes in the company’s fourth-quarter earnings (PDF) Wednesday afternoon. President and CEO Chris Anzalone, Ph.D, said Arrowhead is making progress on the ENaC target, or epithelial sodium channels, which is a potential pathway in cystic fibrosis to rehydrate airway surfaces and improve the work of mucus in the body.

But that progress has not been seen with ARO-ENaC. The company paused a phase 1/2 cystic fibrosis study last year after rats in a preclinical study showed unexpected lung inflammation. Anzalone said Arrowhead “will likely not continue” with the candidate.

Instead, Arrowhead has two or three next-gen compounds in the works to fill the gap. These candidates “appear to have favorable pharmacologic properties compared to ARO-ENaC,” according to the CEO.

“So, we are likely changing horses in the ENaC program, but we have not yet settled on which new horse,” Anzalone said.

The decision to abandon ARO-ENaC was not a surprise to RBC Capital Markets analysts, who pointed out the discontinuation in a note to clients.

Arrowhead’s James Hamilton, M.D., senior VP, discovery and translational medicine, said the preclinical inflammation seen in rats has since been confirmed in nonhuman primates as well.

Hamilton said the problems could have stemmed from an overdose in the preclinical animal studies, which could have been tweaked to find a cleaner toxicity profile for future trials.

“That could provide a faster path back to the clinic, but we decided that the better long-term path is to focus on next-generation ENaC candidates,” he said.

Arrowhead plans to file two new clinical trial applications with the FDA for ARO-RAGE and ARO-MUC5AC in various muco-obstructive and inflammatory pulmonary conditions over the next quarter, according to the CEO. Preclinical data is expected at the American Thoracic Society meeting in May.

Hamilton said that these drugs have been tested at a lower exposure level than the first-generation ENaC program and appear to be more potent. The expectation is that less of the drug can be used with less frequent dosing.

A third application is also expected by the end of the year in an unnamed target and disease area.

https://www.fiercebiotech.com/biotech/arrowhead-changing-horses-for-enac-pulmonary-program-as-phase-1-2-asset-shelved

Long-term care facilities pass 200,000 reported COVID deaths of residents, staff

 Over 200,000 residents and staff at long-term care facilities have died due to COVID-19 over the course of the pandemic, according to a new Kaiser Family Foundation analysis of state and federal agency data.

These deaths account for 23% of all recorded COVID-19 deaths in the nation, down from earlier in the pandemic when long-term care facility (LTCF) deaths accounted for nearly half of all deaths across the U.S., the group wrote.

KFF had tallied 187,000 LTCF deaths from March 2020 to June 2021, when states were regularly reporting data on nursing homes, assisted living, group homes and other LTCF deaths.

Since then, another 14,000 resident and staff deaths among nursing homes have been reported through the federal government.

KFF Senior Policy Analyst Priya Chidambaram wrote that the total of roughly 201,000 LTFC deaths recorded as of Jan. 30 is “likely an undercount” due to limitations in how states and the government have reported these data—for instance, the exclusion of death counts from non-nursing home LTFCs after June 2021.

“Overall, cases and deaths in nursing homes appear to be declining,” Chidambaram wrote in the analysis. “However, this analysis confirms the disproportionate toll of COVID-19 on people living and working in LTCFs and highlights the importance of comprehensive, timely and accurate data.

Chidambaram also noted that data are not available on the demographics or other characteristics of those who died of COVID-19 in LTCFs, precluding analysis on whether factors such as age, race/ethnicity or vaccination status may have played a role in these numbers.

Several investigations have highlighted the disproportionate burden LTFC residents and staff have faced through the pandemic.

An Office of Inspector General report from the summer, for instance, found 2 in 5 Medicare beneficiaries living in nursing homes were diagnosed or likely had COVID-19 during 2020 alone. Another from the U.S. Government Accountability Office found evidence suggesting that most nursing homes had already experienced multiple, often sizable, outbreaks by the end of January 2021.

LTFCs’ latest death count comes as Medicare- and Medicaid-certified nursing homes work to vaccinate staff in accordance with Centers for Medicare & Medicaid Services (CMS) requirements. Roughly 82% of nursing home staff and 87% of residents were fully vaccinated as of Jan. 16, according to CMS.

However, industry groups such as the American Health Care Association and National Center for Assisted Living that generally supported COVID-19 vaccination have raised alarms about the mandate, warning it could exacerbate staffing shortages already jeopardizing care quality and forcing facilities to turn away new admissions.

https://www.fiercehealthcare.com/providers/long-term-care-facilities-surpass-200000-reported-covid-19-deaths-among-residents-staff

Vertex cut to Sector Perform from Outperform by RBC

 Target $269

https://finviz.com/quote.ashx?t=VRTX

Surprise Finding: Prehabilitation Exercise Shrinks Tumor

 In a surprise finding, British researchers report that patients with esophageal cancer who underwent a structured "prehabilitation" exercise program while they were undergoing neoadjuvant chemotherapy showed tumor shrinkage.

Compared to a control group of patients who did not exercise, these patients showed significant tumor regression, and many had their tumor downstaged.

"We were surprised by the strength of the findings," lead author Andrew Davies, MD, PhD, Guy's and St Thomas' Hospitals NHS Trust, London, UK, told Medscape Medical News.

"We were aware of some evidence supporting improved chemotherapy response in animal models, but this was not the primary outcome of interest for the present study," he explained.

"But when the chemotherapy response results started coming through, it became impossible to not notice the differences between the groups."

The study was published online on February 1 in the British Journal of Sports Medicine.

"Tumour downstaging and response to chemotherapy are arguably the most important prognostic factors in esophageal cancer," the team writes.

"That structured exercise programs might contribute to improved cancer regression, possibly through enhanced immunological and/or inflammatory modulation, is potentially clinically significant," they comment.

Study Details

The Pre-EMPT study involved 40 patients with esophageal carcinoma, with 21 patients assigned to a structured prehabilitation exercise program and 19 patients assigned to standard best practice.

Baseline characteristics were comparable between the two groups, and all patients completed four cycles of neoadjuvant chemotherapy with epirubicin, cisplatin, and five fluorouracil (ECF). All patients then underwent surgery.

All patients had a diagnosis of operable adenocarcinoma of the lower esophagus or gastroesophageal junction, and they were all given nutritional, physical activity, and smoking cession advice from specialist nurses, dietitians, and physiotherapists.

Patients assigned to the prehabilitation arm also underwent a moderate intensity physical activity program incorporating aerobic and strength training.

This took place in individualized, "dedicated sessions...five to six times per week" at a gym, Davies explained, giving a total 150 weekly minutes of activity up the last day before surgery.

When the team analyzed all the clinical data, they found

tumor regression (as determined via a score of 1–3 on the Mandard Tumour Regression Grade), was seen in significantly more of the patients in the exercise group (15 of 20 patients, 75%) than in the control group (7 of 19 patients, 36.8%) (P = .025).

On adjusted logistic regression analysis, the exercise intervention was associated with a significantly increased likelihood of tumor regression vs the control arm, at an odds ratio of 6.57 (95% CI 1.52 – 28.30).

Analysis of tissue samples and affected lymph nodes led the researchers to downstage the tumor in nine patients (43%) in the exercise group, compared to three patients (16%) in the control group (P = .089).

"The results from this analysis, showing improvement in pathological regression in the primary tumor and clinical downstaging are hypothesis generating and the first to be demonstrated in a clinical trial in esophageal cancer," the team writes.

However, they caution that these findings come from a small number of patients and that the study was not randomized.

How Is Exercise Working Here?

Davies commented to Medscape Medical News that his "take" on the mechanisms by which exercise could improve tumor control is that they are "likely to be multifactorial and quite complex."

"In simplest terms, there are theories that exercising patients may deliver more blood and oxygen to peripheral tissues, and maybe this extends to delivering a chemotherapy drug to a target tumor," he said.

He noted that the study revealed "some significant differences in body composition and markers of immunity and inflammation," all of which, "at a basic science level, have been associated with chemotherapy response rates."

Patients in the exercise arm were found to have higher median T lymphocyte counts after neoadjuvant chemotherapy vs controls (P = .03), and there were differences in immunity and inflammation markers between the groups, including in interleukin-6, interferon gamma, and tumor necrosis factor alpha.

In addition, patients in the exercise group showed a significant improvement in the Fat Free Mass Index, a measure of body composition, at +2.3% vs -1.9% in the control up (P = .03).

However, Davies emphasized that they do not want to "overstate these relationships," as the differences "remain very interesting and hypothesis-generating."

This work was supported by the Guy's and St Thomas' Charity, London, and the Centre for Health and Human Performance, London. The authors have disclosed relevant financial relationships.

Br J Sports Med. doi:10.1136/ bjsports-2021-104243. Full text

https://www.medscape.com/viewarticle/967737