Terns Flirts with Milestones in Challenging NASH Space

 Today, treatment for non-alcoholic steatohepatitis (NASH), a severe form of fatty liver disease, consists mainly of lifestyle modification – specifically dieting and weight loss. There are no approved drugs that treat it directly, although many are in development.

“One of the key challenges is that multiple different pathways are at play,” Dr. Erin Quirk, M.D., president, CMO and head of R&D at Terns Pharmaceuticals told BioSpace. Inflammation, fibrosis creation and metabolic state of the patient, such as insulin resistance and abnormal signaling between tissues outside the liver, are all factors. “You can’t target one element and make a significant impact. We believe it takes multiple approaches to move the needle.”

Terns is developing a pipeline of single-agent and complementary small molecule therapeutics to address this challenge. TERN-501 is the latest to enter clinical development. It is a thyroid hormone receptor beta (THR-β) agonist that appears to significantly increase levels of sex hormone-binding globulin (SHBG), an important pharmacodynamic marker of THR-β engagement that is linked to NASH histologic efficacy.

TERN-501 could be important in NASH treatment because THR-β agonists can reverse steatosis – the accumulation of excess fat in the liver. “By targeting the beta ISA isoform of the thyroid hormone receptor, which is expressed in the liver, TERN-501 activates fat metabolism locally through upregulation of mitochondrial oxidation to remove fat from the liver. THR- β agonism also likely tones down liver inflammation,” Quirk said.

In a rodent model, low doses of TERN-501 resolved steatosis completely, and reduced serum lipids, hepatic inflammation and fibrosis.

Those improvements seen early on now show signs of being replicated in humans. Results from the recently-completed Phase I clinical trial showed a significant dose-dependent effect of TERN-501 on SHBG. At a 10 mg dosage, TERN-501 resulted in a mean 166% change from baseline in SHBG levels at day 15. The same study showed LDL cholesterol levels dropped a mean of 21%, and the 6 mg dose group achieved a maximum 28% decrease in LDL cholesterol versus an 8% decrease for the placebo group. Meanwhile, mean levels of triglycerides dropped 36% and apolipoprotein-B dropped 28% from baseline at a 10 mg dosage.

Additionally, Quirk added, “The TERN-501 safety profile – to date – is similar to that of placebo,” with no clinically meaningful differences in adverse events or safety laboratories. The drug is highly selective for THR-β. Company literature notes that TERN-501 is “23-fold more selective for THR-β than for THR-α activation in a cell-free assay,” thereby minimizing the risk of cardiotoxicity and other side effects.

Once-daily dosing is supported, and results suggest that TERN-501 eventually could be co-formulated with other small molecule NASH therapeutics, simplifying a daily drug regimen. The drug received Fast Track designation for NASH from the U.S. Food & Drug Administration this past summer.

Because Terns plans a multifactorial approach to NASH treatment, the Phase I study included a drug-drug interaction element in which TERN-501 was co-administered with TERN-101. “TERN-501 potentially addresses liver fat, while TERN-101 is a farnesoid X receptor (FXR) agonist, which may decrease liver scarring and inflammation,” Quirk noted. The results of this portion of the study showed a low potential for drug-to-drug interactions with these two compounds, suggesting their possible use as a combination therapy.

In a separate study, the controlled, 12-week, 100-person Phase IIa LIFT trial showed that TERN-101 began to reverse fibroinflammation and also had a good tolerability profile. In that study, mean corrected T1 (cT1) – a marker of liver inflammation and fibrosis – values showed a decrease of at least 80 milliseconds from baseline in a higher proportion of patients treated with TERN-101 than those treated with placebo. Those decreases indicate significant improvements in fibro-inflammation after treatment with TERN-101. This was the first FXR agonist trial to demonstrate zero discontinuations because of adverse events.

A Phase II combination trial of TERN-501 and TERN-101 is expected to begin in the first half of 2022. The company plans to study each of the two drugs alone and in combination.

“This is a potentially important study,” Quirk said. “It will be the first drug combination Terns will assess, and is likely to be the first time that THR-β and FXR agonists are co-administered to NASH patients. We want to reduce both liver fat and fibroinflammation, so if we can demonstrate a regimen has large effects on cT1 and MRI-PDFF, we may have a chance to see improvements in liver biopsies and in clinical outcomes for patients.”

If such an outcome occurs, it will be a major milestone for treatment advances and for Terns in particular. Quirk observed, “There are few examples of any drug or combination where a high proportion of patients have met those endpoints – resolution of NASH and improvement of fibrosis.”

https://www.biospace.com/article/terns-is-tilting-at-milestones-in-challenging-nash-space-/

Minnesota reports second U.S. omicron Covid case in resident who traveled to NYC

 Minnesota public health authorities confirmed Thursday what appears to be the second U.S. case of the omicron Covid variant in a resident who recently returned from New York City, the state’s department of health said.

The man, who was fully vaccinated and has since recovered, traveled to New York City to attend the Anime NYC 2021 convention at the Javits Center from Nov. 19-21, the department said in a statement. The first omicron case was confirmed in California by U.S. officials Wednesday in a person who recently returned to San Francisco from a trip to South Africa.

New York Gov. Kathy Hochul said they haven’t yet confirmed any cases in the state. “However, we are very cognizant of the fact that it’s very likely soon that someone is going to test positive for this,” she said at a press conference in Manhattan on Thursday.

She said conference attendees were required to get vaccinated, and she recommended that they all get tested.

The patient in California who first tested positive for omicron was also fully vaccinated, has mild symptoms and is improving, Gov. Gavin Newsom said on Wednesday. The person, who is between 18 and 49 years old, had not received a booster dose because they were not six months out from their original vaccination course, he said.

Dr. Mark Ghaly, California’s Health and Human Services secretary, said the fact that the California patient has mild symptoms and is improving underscores the importance of vaccines.

Health officials in the U.S. and around the world are concerned that omicron is more transmissible and may evade the protection provided by currently available vaccines to some degree. The variant has some 50 mutations, more than 30 of which are on the spike protein that the virus uses to attach to human cells.

“The molecular profile of the kinds of mutations that you see [in omicron] would suggest that it might be more transmissible and that it might elude some of the protection of vaccines,” White House chief medical advisor Dr. Anthony Fauci told reporters on Wednesday. “But we don’t know that now.”

The Biden administration on Thursday laid out a plan to combat omicron and a possible winter surge of the predominant delta variant of the virus. The White house is requiring all in-bound international travelers to test for Covid within 24 hours of their departure. The administration is extending mask requirements on domestic flights and public transit through March 18. It is also expanding access to free at-home Covid tests.

The World Health Organization on Wednesday said omicron has been confirmed in at least 23 countries worldwide. The variant was first identified in Botswana last month and brought to the attention of the WHO by public health officials in South Africa.

Maria Van Kerkhove, the WHO’s technical lead, said on Wednesday that hospitalizations are rising in South Africa, but more data is needed before drawing conclusions about whether omicron causes more severe disease.

The CEOs of Pfizer and Moderna say it will take about two weeks to gather enough data to determine what impact omicron’s mutations have on the effectiveness of the current vaccines. They have said it would take until early 2022 to develop a shot that specifically targets the variant. However, Moderna CEO Stephane Bancel said the company can roll out a higher dosage booster shot much quicker.

https://www.cnbc.com/2021/12/02/minnesota-reports-second-us-omicron-covid-case-in-resident-who-traveled-to-nyc.html

Novavax says it could start making Omicron-specific vaccine in January

  Novavax Inc said on Thursday it could begin commercial manufacturing of a COVID-19 vaccine tailored for the Omicron coronavirus variant in January next year, while it tests whether or not its current vaccine works against the variant.

Laboratory data expected in the coming weeks will show whether antibodies from individuals who have previously received Novavax's COVID-19 shot can neutralize the variant, according to the company.

Novavax also said it has started developing an Omicron-specific spike protein antigen and will begin laboratory tests of a new vaccine to target the variant in a few weeks.

The Omicron coronavirus variant has shaken up markets and caused global alarm over concerns about whether it could evade protection provided by widely used vaccines and prolong the public health crisis.

Other vaccine makers including Moderna and Pfizer have also begun working on Omicron-tailored COVID-19 shots.

Novavax's COVID-19 vaccine received its first emergency use approval in Indonesia in early November followed by the Philippines. 

https://finance.yahoo.com/news/novavax-says-could-start-making-153636271.html

Biofrontera gets notice of allowance for pain-reducing protocol patent

 Biofrontera Inc. (Nasdaq: BFRI), a biopharmaceutical company specializing in the commercialization of dermatological products, announced today that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for the U.S. patent application number 17/234,490, titled “Illumination for Photodynamic Therapy,” that covers an innovative, pain-reducing illumination protocol for photodynamic therapy (PDT).

“This patented illumination protocol demonstrates Biofrontera’s commitment to the patients’ need for innovative treatments. The patent also strengthens Biofrontera’s competitiveness for our FDA-approved combination product, Ameluz® together with our PDT-lamp BF-RhodoLED® and its successor model RhodoLED® XL in the U.S. by providing an opportunity to pursue label expansion to include more patient-friendly protocols,” stated Erica Monaco, Chief Executive Officer of Biofrontera Inc.

The patent application claims a method for photodynamic therapy in which a dynamic and innovative illumination protocol is implemented. This protocol consists of changing illumination intensities combined in a predefined order with interruptions of the illumination to specifically modulate and reduce pain perception to the patient. The new illumination protocol aims at combining the high efficacy of Ameluz® with the flexibility of BF-RhodoLED® to modulate light for pain reduction to ultimately become a new standard-of-care in PDT.

Implementation of the protocol to Biofrontera’s medical devices requires a software installation and can be rolled-out to both the BF-RhodoLED® and BF-RhodoLED® XL lamps. To include this illumination protocol in the U.S. prescribing information, Biofrontera Group, in accordance with pipeline development under the license and supply agreement (LSA) between Biofrontera Inc. and Biofrontera AG, will start a Phase 3 trial for the treatment of actinic keratoses on the face and scalp with 3 tubes of Ameluz® and the RhodoLED® XL lamp involving the new protocol in 2022.

https://finance.yahoo.com/news/biofrontera-inc-announces-notice-allowance-141500790.html

BeyondSpring cut to Underperform from Buy by B of A

 Target to $5 from $45

https://finviz.com/quote.ashx?t=bysi&ty=c&ta=1&p=d

Veeva Tumbles On Light 2023 Sales Outlook Despite Quarterly Beat

Medical software company Veeva Systems (VEEV) offered a slightly short view for fiscal year 2023 sales, and VEEV stock plunged late Wednesday.

The dive came hours after officials announced the first Covid case in the U.S. due to the omicron variant. Stocks broadly tumbled. During the regular session, VEEV stock closed at 272.12, down 3.7%. That continued in after-hours trading as shares toppled another 5.2%.

For the fiscal year ending in January 2023, Veeva expects $2.15 billion to $2.17 billion in sales. But that was well below analyst forecasts for $2.185 billion in sales.

VEEV Stock Tumbles On Outlook

Ultimately, third-quarter metrics beat VEEV stock analysts' predictions.

On an adjusted basis, Veeva earned 97 cents a share and reported $476.1 million in sales. Profit climbed more than 24% year over year and beat projections for 88 cents. Sales increased 26% and topped calls for $466 million.

Subscriptions brought in $380.7 million in sales, also up 26% vs. the year-earlier period.

Guidance for fourth-quarter sales came in slightly low, however. Veeva expects $478 million to $480 million in sales. The high end of the guidance touched VEEV stock analysts' call for $480 million. Adjusted profit guidance for 88 cents a share was 2 pennies above estimates.

For the fiscal year ending Jan. 31, Veeva expects adjusted income of $3.69 per share and $1.843 billion to $1.845 billion in sales. The profit outlook handily topped VEEV stock analysts' view for $3.58. The sales guidance was narrowly above forecasts for $1.835 billion.

https://www.investors.com/news/technology/veev-stock-dives-despite-quarterly-beat-as-us-omicron-case-slams-wall-street/

Leerink Partners Stick to Their Buy Rating for Aurinia

 Leerink Partners analyst Joseph Schwartz maintained a Buy rating on Aurinia Pharmaceuticals (NASDAQ:AUPH) on Tuesday, setting a price target of $35, which is approximately 85.77% above the present share price of $18.84.

Schwartz expects Aurinia Pharmaceuticals to post earnings per share (EPS) of -$0.39 for the fourth quarter of 2021.

The current consensus among 5 TipRanks analysts is for a Moderate Buy rating of shares in Aurinia Pharmaceuticals, with an average price target of $33.
The analysts price targets range from a high of $40 to a low of $23.

In its latest earnings report, released on 09/30/2021, the company reported a quarterly revenue of $14.67 million and a net profit of -$50.35 million. The company's market cap is $2.44 billion.

https://www.investing.com/news/leerink-partners-stick-to-their-buy-rating-for-aurinia-pharmaceuticals-2695518