Monday, September 26, 2022
HomeBiotechnologyBioNTech Sees No Bounce from Promising Most cancers Vaccine Knowledge

BioNTech Sees No Bounce from Promising Most cancers Vaccine Knowledge


BioNTech (BNTX) lately took a big step towards life past COVID-19 when it offered some promising information in the course of the latest European Society for Medical Oncology (ESMO) Congress 2022 held in Paris.

Prof. Andreas Mackensen, MD, of College Hospital Erlangen, Germany, offered constructive follow-up information throughout ESMO’s Investigational Immunotherapy Proffered Paper Session from BioNTech’s ongoing Section I/II trial (NCT04503278; 2019-004323-20) assessing its wholly-owned novel chimeric antigen receptor T-cell remedy (CAR-T) candidate BNT211 in sufferers with relapsed or refractory superior strong tumors.

The 21 evaluable sufferers (of twenty-two sufferers total) confirmed a finest total response charge (ORR) of 33% and a illness management charge (DCR) of 67% with one full response, six partial responses and 7 sufferers with steady illness, BioNTech reported.

“Whereas small affected person numbers and early stage of knowledge stop definitive conclusions, our KOL [key opinion leader] is inspired by the profile and is hopeful that the information could mirror positively on the potential for cell therapies in strong tumors,” Invoice Maughan, PhD, a director and Senior Analyst-Biotechnology with Canaccord Genuity, wrote Tuesday in a analysis observe based mostly on opinions from an unnamed “oncology KOL.”

“Additional, the information add pleasure to the potential of most cancers vaccines, which she and her colleagues are keen to review in extra medical trials,” Maughan added.

That pleasure didn’t seem like shared by traders. Between September 9 when the BNT211 information was introduced and yesterday, BioNTech shares slid 6.5%, from $150.91 to $141.05, although shares rose 4% yesterday, to $146.55, after Pfizer stated it dosed the primary sufferers in a Section III research of an RNA-based flu vaccine on which BioNTech stands to gather royalties upon commercialization.

One doubtless motive why traders shied away: The 33% ORR and 67% DCR reported for BNT211 marked a drop from the 43% ORR and 86% illness management charge reported by BioNTech for the vaccine candidate again in April, based mostly on 14 evaluable sufferers within the trial.

BNT211’s therapeutic strategy combines two of BioNTech’s platforms—an autologous CAR-T cell remedy focusing on the oncofetal antigen Claudin-6 (CLDN6) with a CLDN6-encoding CAR-T cell amplifying RNA vaccine (CARVac).

Sufferers acquired CLDN6 CAR-T cells at two dose ranges. Seven sufferers acquired the smaller dose of 1×107 CAR-T cells, together with one affected person who acquired a CAR-T dose beneath dose degree 1. The opposite 15 sufferers acquired the bigger dose of 1×108 CAR-T cells, alone or mixed with CARVac.

Significantly encouraging, in response to BioNTech, have been the medical responses have been seen in sufferers with testicular most cancers handled with the bigger dose:  One full response, three partial responses and two steady illnesses have been seen, representing an ORR of 57% and a DCR of 85%.

Antitumor exercise was increased on the increased dose of CAR-T cells and when mixed with the mRNA vaccine. All 22 sufferers confirmed strong, dose-dependent CAR-T cell growth after infusion with cell frequencies near 109 complete counts within the bigger dose, the corporate stated.

5 of 10 sufferers within the CARVac mixture group confirmed a partial response in comparison with two of 9 sufferers within the monotherapy cohort (CAR-T cell therapy solely—a end result that excluded two sufferers who have been handled with out lymphodepletion.

In June, BNT211 acquired the European Medicines Company (EMA)’s Precedence Medicines (PRIME) designation for the third- or later-line therapy of testicular germ cell tumors.

“This new dataset additional helps the encouraging outcomes we’ve seen for BNT211 to this point,” stated Prof. Özlem Türeci, MD, Co-Founder and chief medical officer at BioNTech. “Along with the lately granted PRIME designation for BNT211 in testicular most cancers it additionally reinforces our technique to mix two of our key expertise platforms in hard-to-treat tumor indications.”

Tumor indications included testicular most cancers (13 sufferers), ovarian most cancers (4), endometrial most cancers, fallopian tube most cancers, sarcoma, gastric most cancers (one affected person every) and one affected person with a tumor of unknown major origin. On the closing date (August 16 for efficacy, June 15 for security), information confirmed the long-term persistence of CAR-T cells noticed in some sufferers for greater than 100 days, and in a single affected person for 200 days.

Hostile occasions, together with cytokine launch syndromes (CRS) and dose limiting toxicities have been manageable. One transient prevalence of neurotoxicity grade 1 and one grade 3 CRS have been noticed that rapidly resolved.

BioNTech causes that the mixture of engineered T cells and mRNA vaccines in a single therapy routine can stimulate and broaden T cells. “This might allow us to develop really highly effective precision immunotherapies,” Türeci said in June.

Akero Therapeutics (AKRO)

Akero shares greater than doubled on Tuesday, rocketing 137% from $12.27 to $29.05 after the corporate launched constructive top-line information from its Section IIb HARMONY trial (NCT04767529) exhibiting that each dosages of its lead product candidate efruxifermin (EFX) met the research’s major endpoint by leading to a ≥1 stage enchancment in fibrosis with out worsening of nonalcoholic steatohepatitis (NASH). The 50 mg dosage confirmed a 41% enchancment, in contrast with 39% for the 28 mg dosage—double the 20% charge proven by placebo.

Akero additionally stated each dosages of EFX met two key secondary endpoints. confirmed NASH decision with out worsening of fibrosis, starting from 3 times the 15% placebo charge for the 28 mg dosage (47%), to about 5 instances for the 50 mg dosage (76%). Additionally, EFX confirmed mixed fibrosis enchancment and determination of NASH at six instances the 5% placebo charge for the 28 mg dosage (29%), and eight instances for the 50 mg dosage (41%).

“We consider immediately’s outcomes from the HARMONY research are an necessary milestone not just for Akero however for your complete NASH group,” Andrew Cheng, MD, PhD, Akero’s President and CEO, stated in a press release. “We consider the information are very compelling and present EFX’s potential to satisfy the essential, world unmet want for sufferers by intervening throughout phases of illness development, doubtlessly addressing each early-stage metabolic drivers and later-stage irritation and fibrosis.”

The corporate is discussing plans for a late-stage research of EFX projected to begin subsequent yr with U.S. and European regulators, Akero chief growth officer Catriona (Kitty) Yale informed analysts Tuesday throughout a convention name.

Akero is one in all a number of firms growing NASH remedies, together with 89bio, Intercept Prescription drugs, Inventiva, Madrigal Prescription drugs, and Novo Nordisk. NASH represents a possible multi-billion-dollar alternative for drug builders, Brian Abrahams, a managing director and Head of Biotechnology Fairness Analysis with RBC Capital Markets, estimated in an investor observe reported by Investor’s Enterprise Each day.

Akero bookended Tuesday’s morning announcement of EFX’s excellent news by disclosing on the finish of the day that it had commenced a $175 million underwritten public providing of its frequent inventory. The corporate is granting underwriters a 30-day possibility to purchase as much as an extra $26.25 million of shares on the public providing worth, minus underwriting reductions and commissions.

J.P. Morgan, Morgan Stanley and Jefferies are appearing as joint book-running managers for the proposed providing. Canaccord Genuity is appearing as lead supervisor and H.C. Wainwright is appearing as co-manager for the proposed providing.

Akouos (AKUS)

Akouos shares climbed 37% earlier this week, paced by a 28% leap on Tuesday from $3.50 to $4.48 after the corporate introduced that it acquired FDA clearance for its Investigational New Drug (IND) utility to start a Section I/II, first in human, pediatric medical trial of its AK-OTOF—the primary time the company has cleared an adeno-associated virus (AAV) vector gene remedy designed to deal with an interior ear situation.

AK-OTOF is a twin adeno-associated viral (AAV) vector-based gene remedy designed to deal with sufferers with OTOF-mediated listening to loss by delivering transgenes encoding OTOF to the interior hair cells (IHCs) of the cochlea. A one-time, unilateral intracochlear administration of AK-OTOF is meant to end result within the expression of regular full-length purposeful otoferlin protein within the IHCs, which has the potential to result in restoration of auditory operate.

The Section I/II trial is designed to guage the protection and tolerability of escalating doses of AK-OTOF administered unilaterally to trial members with OTOF-mediated listening to loss. The research can also be designed to evaluate efficacy by medical measures such because the auditory brainstem response (ABR).

“We count on this to be the primary medical trial for a genetic interior ear situation, the primary through which an AAV gene remedy is run to the interior ear, and the primary for any interior ear situation to start in a pediatric inhabitants,” stated Manny Simons, PhD, MBA, Akouos’ co-founder, President, and CEO.

Jack Okay. Allen, CFA, Senior Analysis Analyst with Baird, is watching intently AK-OTOF in addition to potential head-on competitor DB-OTO, the dual-vector AAV lead gene remedy candidate of Decibel Therapeutics (DBTX). DB-OTO is designed to revive listening to to people with profound, congenital listening to loss attributable to mutations of the otoferlin gene.

“Whereas we consider there are a variety of elementary variations within the design and administration of Decibel’s and Akouos’ candidates, transferring ahead we plan to observe each applications intently as we anticipate preliminary information from both program is more likely to have aggressive readthroughs,” Allen wrote August 31 in a analysis observe.

Altimmune (ALT)

Altimmune shares began Wednesday by plunging 57% earlier than partially recovering, ending the day down 27%. The declines occurred regardless of the corporate reporting constructive topline outcomes from its 12-week Section Ib trial (NCT05006885) of pemvidutide in topics with non-alcoholic fatty liver illness (NAFLD).

Why the disconnect? Attainable causes emerged amongst traders discussing the inventory on Stocktwits. One investor, “AskmeifIcare,” cited analysis notes by Liisa Bayko, a managing director and analysis analyst with Evercore ISI, and Jonathan Wolleben, fairness analysis analyst, biotechnology and biopharmaceuticals with JMP Securities.

Bayko expressed disappointment with the roughly 5% weight reduction in 12 weeks proven within the trial, although the proportion was above that recorded in a research by Novo Nordisk’s marketed drug Rybelsus® (semaglutide). Wolleben stated the proportion was beneath that of an earlier Section I trial of pemvidutide, and beneath the expectations of many traders. Each analysts charge Altimmune shares “Outperform,” with worth targets of $14 a share (Bayko) and $28 a share (Wolleben).

Nonetheless, Jefferies analyst Roger Music, MA, CFA, famous that the 5% weight lack of pemvidutide was consistent with historic outcomes starting from ~4-6% for 2 marketed once-weekly medication: Novo Nordisk’s weight problems therapy Wegovy® (semaglutide) in research for NASH and weight problems, and Eli Lilly’s Mounjaro™ (tirzepatide) in weight problems.

Music stated the excessive percentages of Hispanic sufferers in every therapy arm—figures the corporate quietly disclosed inside an investor presentation of research outcomes—”might have impacted the outcomes”–20 of 23 sufferers dosed with 1.2 mg (87%); 19 of 23 dosed with 1.8 mg (82.6%); 18 of 24 dosed with 2.4 mg (75%); and 14 of 24 placebo sufferers  (58.3%).

“Whereas there aren’t many precedents or mechanistic causes suggesting the correlation, we did discover one information level supporting that Hispanic pts [patients] may do worse in weight reduction vs. non-Hispanic in response to GLP-1 therapy,” Music wrote immediately in a analysis observe. “We’ll anticipate Ph2 weight problems outcomes to raised assess pemvi’s weight reduction efficacy.”

Music added: “It’s too early to write down off pemvi’s potential best-in-class weight reduction efficacy, contemplating: 1) that is an NAFLD vs. weight problems research, with just a few key variations (increased/decrease baseline LFC [liver fat content] /ALT [alanine aminotransferase]) vs. different NAFLD/NASH research; 2) pattern measurement remains to be comparatively small with 12W [12-week] therapy interval; 3) Co has two extra information readouts from a well-designed Ph2 weight problems research (with typical pt baseline vs. different weight problems trials) with long term (24/48W) therapy.”

Pemvidutide—a peptide-based GLP-1/glucagon twin receptor agonist being developed to deal with weight problems and nonalcoholic steatohepatitis (NASH)—met the research’s major efficacy endpoint of statistically vital discount in liver fats content material from baseline in comparison with placebo in all three therapy teams, based mostly on doses of 1.2 mg, 1.8 mg, and a couple of.4 mg, administered weekly for 12 weeks.

On the 1.8 mg dose (with and with out diabetes), pemvidutide achieved a imply discount of liver fats content material of 68.5%, with 94.4% of members attaining a 30% discount in liver fats, 72.2% attaining a 50% discount in liver fats, and 55.6% attaining normalization of liver fats (5% or much less). Imply serum alanine aminotransferase (ALT) ranges declined in all members. In topics with baseline serum ALT above 30 IU/L, ranges declined greater than 17 IU/L in any respect dose ranges and 27.0 IU/L within the 2.4 mg dose cohort.

Pemvidutide additionally met the research’s key secondary efficacy endpoint of statistically vital weight reduction from baseline at 12 weeks of therapy. Altimmune stated imply weight losses of 4.9% (placebo-adjusted 4.7%) in topics with out diabetes and 4.4% in topics with diabetes (placebo-adjusted 3.9%) have been achieved on the 1.8 and a couple of.4 mg doses, respectively.

“We’re happy with the outcomes of this trial, together with the extent of liver fats and serum ALT reductions. Weight reduction was inside our goal vary, and good tolerability was noticed with out the necessity for dose titration,” said Vipin Okay. Garg, PhD, Altimmune’s president and CEO.

Rubius Therapeutics (RUBY)

Rubius shares tumbled 31%, from $1.07 to 74 cents, between Tuesday and yesterday, after the corporate introduced a cost-cutting restructuring that included eliminating 75% of its workforce—about 160 of the 213 staff the corporate reported as of July 31. The job cuts are primarily targeted on medical growth of its two lead candidates, in addition to manufacturing and normal and administrative positions.

“This workforce discount is anticipated to be considerably accomplished in November 2022,” Rubius said in a regulatory submitting. “Moreover, the Firm is exploring the sale of its manufacturing facility in Smithfield, Rhode Island.”

Rubius stated it couldn’t decide how a lot it could document in costs associated to the job cuts, however would accomplish that by an amended submitting or a quarterly report.

The cell remedy firm focuses on growing Pink Cell Therapeutics™ designed to deal with most cancers and autoimmune illnesses. Rubus stated it was restructuring so as to advance a next-generation crimson blood cell-based cell conjugation platform that in response to President and CEO Pablo J. Cagnoni, MD, “has the potential for substantive enhancements over our present platform.”

In consequence, Rubius is halting trials and growth of its two lead candidates. One is its lead oncology program RTX-240, an allogeneic, off-the-shelf cell remedy engineered to concurrently current tons of of hundreds of copies of 4-1BB ligand (4-1BBL) and IL-15TP (trans-presentation of IL-15 on IL-15Rα) of their native types. The opposite candidate being jettisoned is RTX-224, an allogeneic cell remedy engineered to specific tons of of hundreds of copies of 4-1BBL and interleukin-12 (IL-12) on the cell floor.

“Continued funding in our two present medical candidates is not justified,” Cagnoni declared.

He stated the brand new platform held potential for higher efficacy and enhanced versatility, whereas sustaining a positive tolerability profile.

Rubius stated its restructuring will prolong its money runway from mid-2023 to the top of subsequent yr.



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