Shares of Sangamo Therapeutics (SGMO: NASDAQ) surged 69% this past week after the genetic medicines developer announced regulatory progress in its quest to develop its wholly owned gene therapy for Fabry disease—though one analyst maintained that the news posed no significant challenge to the developer of the sole marketed drug for the rare disorder.
Sangamo announced Tuesday that it reached alignment with the FDA on a regulatory pathway to Accelerated Approval for isaralgagene civaparvovec (ST-920) following a successful “Type B” meeting with agency officials in advance of submitting a biologics license application (pre-BLA).
The FDA agreed that Sangamo could use data from its ongoing Phase I/II STAAR trial (NCT04046224) as a primary basis for accelerated approval of isaralgagene civaparvovec—specifically, an intermediate clinical endpoint consisting of the rate of decline in a person’s estimated glomerular filtration rate (eGFR) over time or “eGFR slope” at 52 weeks across all patients.
Sangamo said it will have a complete dataset to support an Accelerated Approval pathway in the first half of next year. Based on that dataset, the company plans to submit a BLA in the second half of 2025, three years ahead of previous estimates. As a result, the company also avoids having to conduct an additional registrational study to establish clinical efficacy.
“I strongly believe in the potential for ST-920 to alleviate many manifestations of Fabry disease and am delighted to have a clear regulatory pathway that could bring this treatment to patients significantly sooner than originally anticipated,” Sangamo CEO Sandy Macrae said in a statement.
Investors more than agreed with Macrae, sending Sangamo shares soaring over two days—from $0.91 a share at the close of trading Monday, jumping 33% to $1.21 on Tuesday and up another 27% to $1.54 Wednesday. The momentum halted Thursday, however, as Sangamo shares fell 3% to $1.49.
Second surge of 2024
The surge marks the second time Sangamo shares have risen dramatically. As StockWatch reported in July, Sangamo shares more than doubled, zooming 120% from $0.40 to $0.88 a share, after the company joined partner Pfizer (PFE: New York Stock Exchange) to report positive Phase III data for their hemophilia A gene therapy candidate giroctocogene fitelparvovec.
Sangamo’s latest announcement raises hopes that development of isaralgagene civaparvovec is back on track, a year after the company said it was deferring additional spending on planning a Phase III program absent a collaboration partner or additional external funding.
In its announcement of the alignment with the FDA, Sangamo disclosed that it had begun to carry out “readiness activities” related to an upcoming BLA, and was “continuing to advance ongoing business development discussions with potential collaboration partners.”
Sangamo can use more cash since its available cash and cash equivalents—$27.8 million as of June 30, plus $50 million upfront from the neuro drug collaboration launched with Genentech, a Member of the Roche Group, in August—give the company a short financial runway that it has acknowledged will only “be sufficient to fund our planned operations into the first quarter of 2025.”
“The company could use a near-term cash infusion to maximize their new pipeline focused on neurological diseases,” Nicole Germino, and Srikripa Devarakonda, PhD, analysts with Truist Securities, observed Tuesday in a research note.
They also cited a damper: “While there is some big pharma interest in rare disease, gene therapy programs such as sickle cell disease have run into challenges on reimbursement, which has curtailed uptake,” Germino and Devarakonda cautioned. They added that some pharma giants have built significant rare disease portfolios, citing Pfizer and Roche (ROG: SIX Swiss Exchange) as well as AstraZeneca (AZN: London Stock Exchange), and UCB (UCB: Euronext Brussels).
Sangamo also offered an update on the STAAR trial, for which it completed dosing in April, with 33 patients dosed. Four years after dosing, the longest-treated patient was successfully withdrawn from Enzyme Replacement Therapy (ERT) in September, one of 18 patients taken off ERT as of Tuesday.
Cautious comments
Sangamo’s good news about its Fabry disease candidate sparked cautious comments from two analysts, who this week emphasized the competitive strength of the first and so far only oral drug approved for the disorder—Galafold® (migalastat), marketed by Amicus Therapeutics (FOLD: NASDAQ).
That’s because the only other treatment options for Fabry disease are two enzyme replacement therapies—Sanofi’s Fabrazyme® (agalsidase beta) and Elfabrio® (pegunigalsidase alfa-iwxj), marketed by Chiesi after it partnered with Protalix BioTherapeutics (PLX: NYSE American) to develop the drug.
“We are not worried since Galafold is standard of care and gene therapies are reserved for late line or tough to treat patients, and the modality hasn’t demonstrated significant commercial traction yet,” Dennis Ding, an equity analyst with Jefferies, wrote Tuesday in a research note. “We see cont’d Galafold growth with naive patients still the biggest oppty.”
During the first half of this year, Galafold generated net product revenues of $210.176 million, up 16% from $180.443 million during H1 2023. Galafold accounted for about 89% of Amicus’ total $237.072 million in net product revenues during January–June 2024.
Joseph P. Schwartz, an analyst with Leerink Partners specializing in biopharma and rare diseases, projected in a research note Tuesday that Galafold will generate between $442 million and $457 million in net product revenues this year, based on Amicus raising its revenue guidance to investors in August to show growth of 14–18% at constant exchange rate (CER) for Galafold.
That’s up from the 13–17% range Amicus projected in May—which itself was an increase from the company’s initial Galafold revenue growth range of 11% to 16%.
“For 3Q24, we assume Galafold sales of $117.4M (vs. consensus of $116.6M). For FY24, we are incrementally above the Street ($453.9M vs. $450.5M),” Schwartz wrote.
Schwartz cited a further potential competitive challenge in Fabry disease: In June, uniQure launched a Phase I/II trial (NCT06270316) for AMT-191, a Fabry disease gene therapy candidate designed to deliver a liver-specific expression of the transgene coding for human a-galactosidase A gene (GLA) to Fabry patients via a single IV infusion. AMT-191 encodes a recombinant serotype 5 based adeno-associated viral vector (rAAV5).
GPCR-unlocking Septerna raises $288M in upsized IPO
The latest entry in this year’s growing parade of first-time public biotechs emerged Thursday when Septerna (SEPN: NASDAQ), a developer of oral small molecule therapies targeting G protein-coupled receptors (GPCRs), raised $288 million in gross proceeds in an upsized initial public offering (IPO).
Septerna sold 16 million shares of its common stock at an IPO price of $18 per share. How much the resulting $288 million gross will translate to in net proceeds isn’t yet confirmed, since the formal IPO Prospectus had yet to be filed and made public Friday at deadline. It will likely exceed the $250 million in net proceeds that Septerna estimated in an amendment to its Form S-1 Registration Statement filed Thursday—an estimated based on the company’s earlier plans to sell 15,277,778 shares.
The company also granted underwriters the offering of a 30-day option to purchase up to an additional 2.4 million shares of its common stock at the IPO price, less underwriting discounts and commissions. Net proceeds from full exercise of the underwriters’ option were estimated at $288.3 million based on the earlier plans.
Septerna develops its drug candidates based on its Native Complex Platform™, designed to unlock the full potential of GPCR therapies by building a pipeline of candidates focused on endocrinology, immunology, and inflammation, and metabolic diseases.
The company has disclosed four pipeline candidates, one of which has advanced into the clinic—SEP-786, a PTH1R agonist designed to treat the rare endocrine disease hypoparathyroidism now under study in a Phase I trial. “We expect to report data from this trial in mid-2025,” Septerna stated in its registration statement.
Also in Septerna’s pipeline are three preclinical programs:
- SEP-631—A selective, oral small molecule MRGPRX2 negative allosteric modulator (NAM) being developed initially to treat chronic spontaneous urticaria (CSU). “We have initiated IND-enabling studies of SEP-631 and upon completion, we anticipate submitting for regulatory clearance to initiate a clinical trial.” SEP-631 could also be developed for the treatment of other mast cell diseases, Septerna added.
- TSHR NAM—An oral small molecule thyroid stimulating hormone receptor (TSHR) NAM being developed to treat Graves’ disease and thyroid eye disease: “We are advancing several lead compounds toward the selection of a development candidate for IND-enabling studies.”
- Incretin programs–Next-generation, oral small molecules envisioned as selective single- or multi-acting glucagon-like peptide 1 (GLP-1) receptor agonists: “We are advancing several lead compounds toward the selection of one or more development candidates for IND-enabling studies.”
Interest in IPOs has grown in recent weeks, reflected in part by the successful offering of BioAge Labs (BIOA: NASDAQ) and planned listing of Orum Therapeutics (475830; KOSDAQ).
BioAge raised $227.7 million in gross proceeds through its IPO, in which an initial 11 million shares were sold at $18 a share on the Nasdaq Global Select Market—followed by underwriters exercising in full their option to purchase 1.65 million additional shares at the IPO price.
Orum has revealed plans to raise between KRW 90 billion ($64.8 million) and KRW 108 billion ($77.8 million) by selling three million shares at between KRW 30,000 ($21.60) and KRW 36,000 ($25.92).
Leaders and laggards
- Alto Neuroscience (ANRO: New York Stock Exchange) shares plunged 72% over two days, from $14.53 Tuesday to $4.13 Thursday, two days after the company said its ALTO-100 failed a Phase IIb trial (NCT05712187) assessing the drug in major depressive disorder (MDD) by missing its primary endpoint of statistically significant change from baseline vs. placebo on the Montgomery-Åsberg Depression Rating Scale (MADRS) at the end of the six-week treatment period. ALTO-100 also did not demonstrate benefit over placebo on pre-specified key secondary analyses—nearly two years after Alto trumpeted positive Phase IIa results. Alto said it expected to complete analysis of the study’s full dataset to determine “most appropriate” next steps to further evaluate ALTO-100 in MDD. ALTO-100 is also being studied as an adjunctive treatment in a Phase IIb study in bipolar depression.
- Intellia Therapeutics (NTLA: NASDAQ) shares tumbled 20.5% from $19.94 to $15.85 Thursday, after the company published online in The New England Journal of Medicine Phase II data from its ongoing Phase I/II trial (NCT05120830) assessing the in vivo CRISPR-based gene editing therapy candidate NTLA-2002 in hereditary angioedema (HAE). Intellia reported that mean monthly attack rates compared to placebo fell by 75% and 77% for the 25 mg and 50 mg arms during weeks 1–16, and by 80% and 81% during weeks 5–16, respectively. Intellia said its data showed NTLA-2002 could eliminate HAE attacks after a one-time infusion. However, Baird analyst Jack K. Allen lowered his firm’s 12-month price target on Intellia shares 25%from $24 to $18, asserting that the benefit of reduced attacks may be outweighed for investors by the risks of in vivo gene editing and the availability of numerous other HAE candidates in development.
- Marinus Pharmaceuticals (MRNS: NASDAQ) shares cratered 82% from $1.69 to $0.30 Thursday, after the company said it was halting further clinical development of ganaxolone and was taking steps to reduce costs that include a reduction in its workforce. The moves came after Marinus acknowledged that the oral neuroactive steroid GABA A receptor modulator failed the Phase III TrustTSC trial (NCT05323734) assessing the drug in children and adults with seizures associated with tuberous sclerosis complex (TSC). Ganaxolone did not meet the primary endpoint of percent change in 28-day TSC-associated seizure frequency—and while reductions in seizure frequency favored the ganaxolone arm, the primary endpoint did not achieve statistical significance, Marinus said. Shares rebounded 37% to about $0.41 Friday. Marinus markets ganaxolone as Ztalmy® for the treatment of seizures associated with CDKL5 deficiency disorder in patients two years of age and older.
- Monopar Therapeutics (MNPR: NASDAQ) shares multiplied more than seven-fold (605%) from $4.63 to $32.66 Thursday, after the company announced it secured an exclusive worldwide license from Alexion, AstraZeneca Rare Disease, to develop ALXN-1840 (bis-choline tetrathiomolybdate), a drug candidate for Wilson disease that Alexion had progressed through the 214-patient Phase III FoCus trial (NCT03403205), which met its primary endpoint. Last year, Alexion terminated its program to develop ALXN-1840 in Wilson disease, after a review of results from earlier Phase II mechanistic trials and discussions with regulators. Monopar said it will be responsible for all future global development and commercialization activities for ALXN-1840 going forward. However, Monopar shares fell back to earth Friday, nosediving 48% to $16.93, followed by a further 5% drop in after-hours trading, to $16.02.
- Qualigen Therapeutics (QLGN: NASDAQ) shares plummeted 38% from $0.17 to %0.11 Thursday after the company announced the September 23 resignations of its CEO and chairman Michael Poirier, and its CFO Christopher Lotz. “Both resignations were attributed to disagreements with the company regarding its future direction and strategic initiatives,” Qualigen stated. In the days that followed, Qualigen’s board named Campbell Becher as president and Kevin Richardson as interim CEO and CFO. Richardson previously served as CEO of Sanuwave Health, a medical device startup that grew during his tenure to $20 million in revenue. Qualigen’s shares rebounded 12% on Friday, to $0.12.
