As biotechs faced investors at the J.P. Morgan Healthcare Conference this week, they emphasized agreement with the FDA on clinical trial design and regulatory pathways to approval. Atara, meanwhile, lamented the agency’s “complete reversal of position” after its therapy for a rare surgical complication was rejected.
Last year, a clutch of biotechs experienced regulatory whiplash as previous FDA guidance was seemingly reversed, leading to rejections or delayed timelines. This trend continued into 2026, as Atara Biotherapeutics on Monday announced an FDA rejection it described as “a complete reversal of position.”
Amid this regulatory uncertainty, several biotechs wanted to make it crystal clear during the J.P. Morgan Healthcare Conference this week that their alignment with the regulator was rock solid. Beam Therapeutics, Cabaletta Bio, PTC Therapeutics and BridgeBio all communicated alignment with the FDA on regulatory pathways or next steps for their programs, according to analyst notes dispersed throughout the week as companies provided updates at JPM26.
H.C. Wainwright analysts highlighted regulatory alignment as a key theme throughout the meeting. “Regulatory alignment is compressing timelines and improving visibility to value inflections,” the firm wrote in a Wednesday morning note.
Nevertheless, Atara’s Monday news demonstrates that biotech is not out of the woods of FDA uncertainty just yet. In its complete response letter, for the proposed use of Ebvallo in treating a serious post-transplant complication related to the Epstein-Barr virus, the FDA said Atara’s single-arm ALLELE study was “no longer considered to be adequate to provide evidence of effectiveness for accelerated approval,” according to Atara’s announcement. The company further noted that the agency’s “new position is contrary to the FDA’s prior guidance to Atara, the FDA’s alignment with Atara on the clinical trial data set, and the acceptance of the trial design as a single arm study as relevant for this patient population at BLA submission.”
The chief executives of Replimune and Capricor shared similar sentiments after rejections last year.
Speaking on a BioSpace webinar in November, BMO Capital Markets analyst Evan Seigerman spoke to this trend, specifically pointing to Replimune, which in July was hit with a surprise rejection for its advanced melanoma candidate RP1.
“Today, they had one set of guidance from FDA with regard to clinical trial design, or how they could have a unique trial design . . . and then all of a sudden, there’s a 180,” Seigerman said of the company’s experience, “and it throws everything into a tailspin.”
Beam, Cabaletta, PTC and BridgeBio are hoping for better luck. Here is how their regulatory pathways are lining up as they embark on 2026.
Beaming Up to an Accelerated Pathway With AATD Alignment
Beam Therapeutics, which is taking key steps this year to transition to a commercial-ready company, announced that it has aligned with the FDA on a potential accelerated approval pathway for BEAM-302 in alpha-1 antitrypsin deficiency (AATD). The investigational gene editor showed positive early results in a Phase I/II trial in March 2025, demonstrating the first-ever genetic correction in the rare disease, which is characterized by no or insufficient expression of the AAT protein.
The accelerated pathway for BEAM-302 will be based on AAT biomarkers evaluated over 12 months, Beam said in a press release issued Jan. 11, two days before the company’s presentation at JPM26. The company plans to enroll around 50 additional patients who will be treated with the optimal biologic dose in an expansion of the Phase I/II study.
“We believe this defined regulatory path for BEAM-302 significantly de-risks development,” Wainwright analysts wrote on Wednesday.
Beam’s autologous cell therapy for sickle cell disease (SCD), risto-cel, is even closer to the regulatory finish line, with the company expecting to file a biologics license application by the end of 2026.
Cabaletta Reaches Consensus With FDA on Registrational Lupus Cohorts
Meanwhile, Cabaletta Bio has reached alignment with the FDA on new registrational cohort designs for its CD19 CAR T cell therapy rese-cel in Phase I/II trials in systemic lupus erythematosus (SLE) and lupus nephritis (LN). However, the plan involves the use of single-arm cohorts, which have been a point of contention in some of the FDA’s seemingly inconsistent guidance.
Under the agreed-upon design, rese-cel will be evaluated in two independent, single-arm cohorts, one comprising patients with non-renal SLE and the other made up of patients with LN, according to Cabaletta’s Jan. 12 press release. Each cohort will include approximately 25 patients.
Cabaletta is even further along with rese-cel in dermatomyositis (DM) and antisynthetase syndrome (ASyS), as the biotech launched these “FDA-aligned” registrational cohorts in December.
“In our view, Cabaletta continues to execute on advancing rese-cel in multiple indications, as highlighted by the initiation” of this registrational trial, William Blair analysts said in a Monday note.
And Cabaletta is expecting complete Phase I/II data from rese-cel in SLE, systemic sclerosis (SSc) and myasthenia gravis (MG) in the first half of 2026, according to its announcement.
“While we believe the company has several opportunities in 2026 for value creation, the most critical will likely be potential regulatory alignment in SSc and MG and updated clinical data from its trials without preconditioning,” William Blair said on Monday.
PTC Gives Positive Huntington’s Update After Mixed Phase II Reaction
PTC Therapeutics had a mixed 2025 from a regulatory standpoint.
In July, the rare disease–focused biotech won FDA approval for Sephience for children and adults with phenylketonuria (PKU). However, in August the FDA rejected the company’s Friedreich’s ataxia candidate, vatiquinone, saying in its CRL that “substantial evidence of efficacy was not demonstrated.”
In a press release issued ahead of CEO Matthew Klein’s JPM presentation on Jan. 12, Klein lauded the approval and “strong start to the global launch” of Sephience.
Earlier in the pipeline, PTC is developing votoplam for Huntington’s disease. On Monday, the company announced it had aligned with the FDA on design of a global Phase III trial, which it plans to initiate in the first half of this year. During the end-of-Phase II meeting, held during the fourth quarter last year, the FDA also confirmed its openness to a potential accelerated approval pathway for the asset, PTC said, given the significant unmet need in Huntington’s.
PTC518, a small molecule that includes a premature stop codon in the huntingtin (HTT) mRNA, lowered blood HTT protein levels by 23% at the lowest dose in the Phase II PIVOT-HD trial, PTC reported in May 2025. Earlier-stage patients also saw functional improvements.
While the trial met its primary endpoint, analysts were less than impressed. Willliam Blair at the time noted that patients with later-stage disease did not show any functional benefit on PTC518 and protein reduction in cerebrospinal fluid was less robust in these patients.
In a note to investors on Monday, William Blair analysts said they “view alignment with the FDA on the trial design for votoplam in Hungtinton’s [sic] disease as positive, and look forward to the company sharing additional details regarding the trial’s design and what endpoints could be used to support accelerated approval.”
BridgeBio’s Muscular Dystrophy Drug on Track for Traditional Approval
Everything is coming up roses for BridgeBio, which delivered what Truist Securities in a Monday note called a “surprise beat” for transthyretin amyloid cardiomyopathy (ATTR-CM) drug Attruby in Q4, 2025. The $146 million in revenue, reported during the company’s JPM presentation on Jan. 12, represented a growth of 35% quarter-on-quarter, according to Truist.
On the regulatory front, BridgeBio reported that two end-of-Phase II meetings with the FDA had taken place, for encaleret in chronic hypoparathyroidism and ribitol in limb girdle muscular dystrophy type 2I/R9 (LGMD2I/R9).
For ribitol, BridgeBio suggested that the FDA indicated alignment on pursuing traditional full approval in LGMD2I/R9 based on positive functional data at the trial’s interim analysis, according to Truist. The company plans to submit new drug applications for both assets to the FDA in the first half of 2026.
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