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Af­ter a slow cou­ple of weeks, the biotech IPO mar­ket is heat­ing back up with four more com­pa­nies hit­ting Nas­daq.

In­stil Bio, Con­nect Bio­phar­ma, Finch Ther­a­peu­tics and Gain Ther­a­peu­tics are this week’s win­ners, with the fear­some four­some all mak­ing their pub­lic de­buts Thurs­day or Fri­day. In­stil led the way with a heav­i­ly up­sized $320 mil­lion raise, mark­ing the sec­ond-biggest IPO raise of 2021 be­hind Sana, and Con­nect and Finch al­so pulled in nine-fig­ure fund­ing.

By the End­points News tal­ly, there have been 22 com­pa­nies to com­plete their IPO rais­es so far in 2021. The group has com­bined to raise about $3.81 bil­lion.

In terms of ac­tiv­i­ty, noth­ing will like­ly top the first week of Feb­ru­ary any­time soon when 10 — yes, 10 — biotechs made the pub­lic leap. But this week’s four de­buts mark the sec­ond-busiest IPO week of the year.

With $320M megaraise, In­stil seeks to make its mark in the TIL space

In­stil had orig­i­nal­ly pen­ciled $100 mil­lion in­to their S-1, but it soon be­came ap­par­ent they had a much high­er raise in mind.

Ear­li­er this week, the Dal­las com­pa­ny up­sized its es­ti­mate to $250 mil­lion and in­creased its po­ten­tial range from $17-$19 to $19-20 per share. They ul­ti­mate­ly priced at $20, the high end of the new range, and pulled in the $320 mil­lion raise.

Pre-IPO, In­stil $TIL had raised $380 mil­lion in ven­ture fund­ing.

In­stil faces some high-pro­file com­pe­ti­tion not just with TIL play­ers like Io­vance, Adap­ti­m­mune and PACT Phar­ma, but al­so CAR-T and TCR-T cell ther­a­py de­vel­op­ers like Gilead’s Kite and Bris­tol My­ers Squibb’s Juno. But they’re all-in on their tech plat­form, and be­lieve they have the prop­er man­u­fac­tur­ing ca­pa­bil­i­ties to boot.

The com­pa­ny plans to sub­mit its first IND to the FDA lat­er this year and head straight in­to a Phase II tri­al for melanoma with its lead TIL can­di­date, ITIL-168. In­stil is hope­ful that could lead to a sub­mis­sion for ap­proval some­time in 2023.

But giv­en the CMC is­sues that seem to trip up every gene ther­a­py play­er nowa­days, In­stil like­ly faces a long road ahead.

Con­nect looks to si­dle up to the com­pe­ti­tion — and Dupix­ent is up first

Con­nect Bio­phar­ma came up with the sec­ond-high­est raise of this week’s group, net­ting $191 mil­lion in their IPO haul.

The fig­ure is slight­ly high­er than the terms they set out late last week, when Con­nect $CNTB es­ti­mat­ed $150 mil­lion in a $15 to $17 share range. Ul­ti­mate­ly, the Chi­nese com­pa­ny priced at the high end of that spec­trum: $17.

Con­nect’s IPO comes af­ter the old pals from a uni­ver­si­ty in Guangzhou, Chi­na who found­ed the biotech se­cured a $115 mil­lion Se­ries C last Au­gust. As they tran­si­tion to be­com­ing a pub­lic com­pa­ny, they come with a pipeline of im­mune mod­u­la­tors.

Their port­fo­lio is led by an an­ti-IL-4Ra an­ti­body that they hope can treat in­flam­ma­to­ry al­ler­gic dis­eas­es such as atopic der­mati­tis, asth­ma, and chron­ic rhi­nos­i­nusi­tis with nasal polyps — mar­kets that have seen big in­vest­ment from world’s biggest phar­ma com­pa­nies. Con­nect’s lead ex­per­i­men­tal drug hits the same tar­get as Re­gen­eron and Sanofi’s Dupix­ent.

How will their pro­gram match up? All eyes are on a Phase IIb tri­al ex­pect­ed to read out topline da­ta in the sec­ond half of 2021. Con­nect be­lieves the as­says they used in drug dis­cov­ery could make them a best-in-class con­ten­der.

Finch hopes to move past the strug­gles of the mi­cro­bio­me field

Finch Ther­a­peu­tics al­so raised more mon­ey than orig­i­nal­ly es­ti­mat­ed. Af­ter pen­cil­ing $100 mil­lion in­to their S-1, Finch re­turned from the IPO well with a $128 mil­lion raise.

They al­so priced at the high end of their range, de­but­ing on the mar­ket Fri­day at $17 per share. The pub­lic de­but comes rough­ly six months af­ter its $90 mil­lion Se­ries C round.

Born from the ash­es of an im­plo­sion at Seres Ther­a­peu­tics that cloud­ed the mi­cro­bio­me field in 2017, Finch $FNCH is fo­cus­ing its re­search on an oral ther­a­py pro­gram that can de­liv­er a com­plete mi­cro­bio­me to the gut. The can­di­date, CP101, is be­ing test­ed in pa­tients with a C. dif­fi­cile in­fec­tion and has so far re­turned pos­i­tive re­sults for re­cur­rence-free bac­te­ria clear­an­ce.

A sec­ond tri­al for the pro­gram is ex­pect­ed to be­gin not long af­ter the IPO, with topline da­ta ex­pect­ed some­time in 2023. The study will like­ly have a sim­i­lar de­sign and size to the ear­li­er tri­al. Among 206 pa­tients, pa­tients giv­en CP101 had a 74.5% chance of re­cur­rence-free bac­te­ria clear­ance ver­sus 61.5% on the place­bo arm.

The com­pound it­self is a cap­sule made of freeze-dried stool sam­ples from healthy donors. The biotech is al­so plan­ning oth­er clin­i­cal stud­ies in chron­ic he­pati­tis B, in­flam­ma­to­ry bow­el dis­ease and autism spec­trum dis­or­der.

Gain goes pub­lic with pro­tein mis­fold­ing pro­grams

Gain pulls up the rear this week, suc­cess­ful­ly rais­ing the $40 mil­lion they orig­i­nal­ly out­lined in their S-1. The biotech priced at the mid­point of its range, de­but­ing Thurs­day at $11 per share.

Gain $GANX fo­cus­es on pro­tein mis­fold­ing, with an ini­tial goal of treat­ing lyso­so­mal stor­age dis­or­ders. They have ex­clu­sive­ly in-li­censed a pro­pri­etary plat­form to ac­com­plish this, and are tar­get­ing the GLB1 gene to cre­ate ther­a­pies for GM1 gan­gliosi­do­sis and the GBA1 Gauch­er’s dis­ease and Parkin­son’s.

As de­scribed in their SEC pa­per­work, the biotech is plan­ning to di­rect its IPO funds to­ward these can­di­dates, hope­ful­ly push­ing them in­to Phase I/II tri­als for their re­spec­tive in­di­ca­tions. Gain emerged from stealth last Ju­ly with a $10 mil­lion Se­ries B round, us­ing that fundraise to set up two IND-en­abling stud­ies.

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

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Another day, another SPAC vying for a spot on Nasdaq.

On Wednesday, OncoSec Medical CEO Daniel O’Connor filed the S-1 paperwork for a new blank-check company he’s leading called Larkspur Health Acquisition. The former Advaxis chief penciled in a $75 million raise, with plans to offer 7.5 million shares at $10 apiece.

The Biomedical Advanced Research and Development Authority is cooling its jets in looking for new, potential Covid-19 treatments, at least in the near term.

An HHS spokesperson told Endpoints News via email, “to date, BARDA has obligated more than $9 billion for the development and/or purchase of 13 therapeutics, beginning in February 2020 with support to develop Regeneron’s monoclonal antibody therapeutic. Therapeutics are an important element of the COVID-19 response, and we are focused on the programs currently underway and/or in negotiation using the funds available to us.”

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.