Instil Bio’s upsized IPO raises $320M for clinical tests of TIL cancer cell therapy

 

The cell therapy technology that underpins Instil Bio has treated fewer than two dozen patients in the past decade—all of them under compassionate use. In the three years since the cancer drug developer launched, it has leveraged the limited clinical data into $380 million in funding. Now it has $320 million more from its IPO.

Instil was able to sell more shares and at a higher price than it initially planned. The Dallas-based company set preliminary IPO terms on Monday for an offering of 13.9 million shares in the range of $17 to $19 each. On Thursday, the biotech boosted the deal size and ended up pricing its offering of 16 million shares at $20 each, the top end of its revised price range. Those shares will trade on the Nasdaq under the stock symbol “TIL.”

Instil is developing a type of cancer cell therapy called tumor-infiltrating lymphocytes, or TILs. These cells are immune cells that have invaded the patient’s tumors and can recognize and kill the patient’s cancer cells. TIL therapy is made by removing these immune cells from the tumor, multiplying those cells in a lab, and infusing them back into the patient.

Cell therapies made from a patient’s own immune cells have already secured FDA approval. Novartis and Gilead sciences market such treatments, known as CAR-T therapies. But Instil says in its prospectus that TILs offer advantages compared to their CAR-T cousins. Unlike CAR-T, which targets a single tumor antigen, TIL therapy can recognize a broad set of antigens unique to the patient. That capability allows the treatment to address the diversity of antigens expressed by each patient’s tumors.

TIL therapy dates to 1988, when a small National Cancer Institute study successfully applied the cell therapy to 20 patients who had metastatic melanoma. Since that study, additional research has found that TILs can also treat other types of solid tumors. But Instil says in its prospectus that the challenge of manufacturing TIL therapy has limited its use to academic centers or compassionate use.

Prior to Instil’s founding, its TIL technology was used for therapies administered under compassionate use at The Christie, a Manchester, U.K.-based hospital that is the largest cancer care center in Europe. The hospital’s TILs were manufactured by Immetacyte, a University of Manchester cell therapy spinout.

The Christie administered its Immetacyte-manufactured TILs to patients from 2011 to 2019. According to the IPO filing, of the 21 patients treated under compassionate use, four showed complete remission of their cancers. Partial remission was observed in 10. Instil said that four patients reported stable disease. A total of 10 patients have since died from complications that arose as their disease progressed.

Instil licensed Immetacyte’s TIL technology in 2019. Last March, Instil acquired Immetacyte outright, bringing that company’s manufacturing capability in-house. As is the case with many cell therapies, manufacturing poses logistical challenges. In the academic research settings where TIL therapy was first developed, the operating room where a patient underwent the procedure was close to the laboratory where the therapy was made, the company said in its IPO filing. But in a global clinical trial, that process becomes more complex.

Instil has developed a proprietary process to cryopreserve surgically removed tissue at a regional hub close to a clinical site. Those samples will then be shipped to one of two Instil manufacturing sites, one in Manchester and the other in the Los Angeles area. The company plans to spend $150 million of the IPO proceeds on those sites, according to the prospectus.

Clinical data from The Christie’s compassionate use program will be the basis of Instil’s application seeking the FDA’s go-ahead to begin clinical testing of its lead TIL candidate, ITIL-168, in a Phase 2 study in advanced melanoma. If cleared to proceed, Instil expects that study will begin in the second half of this year. The company has budgeted $250 million from the IPO proceeds to take ITIL-168 through Phase 2 testing. Preliminary safety and efficacy data could be ready in 2023. If the study is successful, Instil believes the data could support a submission seeking FDA approval.

Instil also plans to start Phase 1 tests of its lead TIL therapy in other types of cancer including cutaneous squamous cell carcinoma, non-small cell lung cancer, head and neck squamous cell carcinoma, and cervical cancer. Those studies could begin in the first half of 2022. Instil estimates that the IPO cash and its current cash holdings will fund operations into 2023.

The Instil pipeline includes a TIL genetically engineered with the company’s co-stimulatory antigen receptor (CoStAR) technology. This engineering enhances the immune cell to express molecules that bind to tumor-associated antigens and stimulate T cells in the tumor microenvironment. The company believes this capability could help patients with cancers that have historically resisted immunotherapy. Instil plans to spend $50 million of its IPO cash on its lead CoStAR TIL, ITIL-306, with the goal of starting Phase 1 testing next year.

Instil’s largest shareholder is CEO Bronson Crouch, who owns 34.2% of the company after the IPO, according to the filing. Crouch is also the founding partner of Curative Ventures, which led the company’s 2017 Series A financing and is Instil’s largest institutional shareholder, owning a 30.2% post-IPO stake.

Cancer immunotherapy is a competitive field, even within the niche of TIL therapy. Instil is chasing Iovance Biotherapeutics, which has advanced its TIL, lifileucel, to a pivotal Phase 2 study. The San Carlos, California-based company has said it expects to seek FDA approval this year in metastatic melanoma. Other TIL competitors include Adaptimmune Therapeutics, Achilles Therapeutics, and Intima Bioscience.

Finch Therapeutics fetches $127.5M in stock market debut

Finch Therapeutics upsized its IPO, raising $127.5 million to fund development of its microbiome drug pipeline, including a program set to begin pivotal testing later this year. On Monday, Finch set terms for an offering of 6.25 million shares priced in the range of $15 to $17 each. On Thursday, the company kept the price range but boosted the offering to 7.5 million shares. The company priced its IPO at $17 per share. Those shares now trade on the Nasdaq under the stock symbol “FNCH.”

Somerville, Massachusetts-based Finch aims to treat disease by delivering a complete, healthy microbiome to patients in the form of a capsule. The company’s therapies are made from stool samples collected from healthy donors. Those samples are crystallized then milled into a powder that is encapsulated. The goal of the treatment is to restore a patient’s microbiome to a healthy state.

Finch’s lead program, CP101, is a potential treatment for recurrent Clostridioides difficile (C. diff) infection. These bacteria are normally found in the gut, but antibiotics can disrupt the healthy balance, allowing C. diff bacteria to proliferate and cause infection. Last June, Finch reported results from a Phase 2 test of CP101 showing that the microbiome drug met the main goal of achieving a clinical cure after eight weeks. The company now plans to start a Phase 3 study in the middle of this year. About $50 million of the IPO proceeds are set aside for funding this study.

Finch is developing treatments for other disorders associated with the gut microbiome. The company plans to spend $20 million of the IPO proceeds on clinical tests of FIN-211 as a treatment for autism spectrum disorder. Another $10 million is earmarked for tests of CP101 in other diseases, including hepatitis B virus. Finch also plans to spend $60 million on its discovery technology that identifies diseases caused by an unbalanced microbiome and designs microbiome therapies to address them.

In addition to its internal research, Finch has a research alliance with Takeda Pharmaceutical focused on inflammatory bowel diseases. Takeda has licensed two Finch microbiome candidates. Finch plans to start clinical tests of FIN-524 in ulcerative colitis in the first half of next year. The preclinical tests leading up to a human study could begin for FIN-525 in Crohn’s disease in the second half of this year, pending a review by Takeda.

Gain grabs $40M to bring “STAR” small molecules to clinic

Gain Therapeutics priced its offering of more than 3.6 million shares at $11 apiece, which was the midpoint of its $10 to $12 per share price target. On Thursday, Those shares began trading on the Nasdaq under the stock symbol “GANX.”

Bethesda, Maryland-based Gain is developing small molecule drugs that bind to a protein’s allosteric sites, regions are far from the active site where molecules typically attach. The company has proprietary technology, Site-Directed Enzyme Enhancement Therapy (SEE-Tx), which it uses to discover allosteric sites on misfolded proteins. The compounds yielded by the platform are called Structurally Targeted Allosteric Regulators or “STARs.”

The company has two lead programs, both for rare, inherited enzyme deficiencies. The first is for Morquio B and GM1 Gangliosidosis, both of which are caused by a deficiency of an enzyme called GLB. In its prospectus, Gain said it would use between $7 million and $9 million of the IPO proceeds to advance a drug into Phase 1/2 testing.

The other program is in development for neuronopathic Gaucher disease, a deficiency of an enzyme called GCase. That genetic mutation that leads to this type of Gaucher is also at the root of a severe form of Parkinson’s disease. Gain aims to treat both diseases by restoring the enzyme’s function. Between $11 million and $14 million is planned for advancing this research into Phase 1/2 testing.

Gain was founded in 2017 by Khalid Islam, who serves as the company’s chairman. Islam is the former CEO of Gentium, which was acquired by Jazz Pharmaceuticals for $1 billion in 2013. Gentium had developed defibrotide, a treatment for veno-occulsive disease, a liver condition. The FDA approved defibrotide in 2016 and Jazz markets it under the name Defitelio.

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