A pair of cancer immunotherapy developers applying their own T-cell technologies are ringing out 2018 with filings for a combined up-to-$186 million in initial public offerings they aim to complete in the new year.

TCR2 Therapeutics disclosed plans to raise up to $100 million in gross proceeds through an IPO, according to an S-1 registration statement filed by TCR2 with the U.S. Securities and Exchange Commission on Friday.

A day earlier, an S-1 registration statement filed by Harpoon revealed that it planned to raise up to $86.25 million gross.

Neither company has yet to spell out how much they would set aside toward any of several purposes outlined in their preliminary prospectuses.

TCR2 aims to develop T-cell therapies for cancer based on its TRuC™ (TCR Fusion Construct) T cells, designed to harness the natural T-cell receptor complex to recognize and kill cancer cells using the full power of T-cell signaling pathways independent of human leukocyte antigen (HLA).

According to its filing, TCR2 intends to use its IPO proceeds in part toward funding the development of its lead solid tumor candidate TC-210—designed to target mesothelin-positive solid tumors—through the completion of its planned Phase I/II trial in patients with mesothelin-positive non-small cell lung cancer, ovarian cancer, malignant pleural mesothelioma, and cholangiocarcinoma.

TC-210 is TCR2’s most advanced TRuC-T cell product candidate. The company has cited preclinical studies in which TC-210 has shown better anti-tumor activity and persistence of TRuC-T cells compared to CAR-T cells while also exhibiting lower levels of cytokine release.

IND Filing Planned for 2019

TCR2 conducted a pre-IND meeting with the FDA in February 2018, and said in its preliminary prospectus that it expects to file an IND for TC-210 early in the new year.

TCR2 said it also plans to use its IPO proceeds to fund:

  • Development of its lead blood cancer candidate TC-110, a mono TRuC-T cell designed to target CD19-positive B-cell hematological malignancies, through a Phase I trial. TCR2’s clinical development plan for TC-110 will initially focus on adult acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL).
  • Development of TC-220, a mono TRuC-T cell, for the treatment of patients with MUC16-positive ovarian cancer through a Phase I/II clinical trial. The company notes that MUC16 is highly expressed in other solid tumors, including pancreatic, gastric, and colorectal cancer.
  • Manufacturing activities to support all three planned trials

TCR2 said any remaining proceeds will be used for funding new and ongoing R&D, the company’s product platform, working capital, and other general corporate purposes—which according to the company may include funding for the hiring of additional personnel, capital expenditures, and the costs of operating as a public company.

TCR2 plans to trade its shares on the NASDAQ Global Market under the symbol “TCRR.”

TCR2’s registration statement disclosed a net loss of $16.561 million in the first nine months of 2018 compared with $9.058 million for January-September 2017. For all of 2017, TCR2 reported a net loss of $13.070 million, compared with a net loss of $9.915 million in 2016.

Headquartered in Cambridge, MA, TCR2 launched in December 2016 after securing $44.5 million in Series A financing led by MPM Capital and F2 Ventures. According to Crunchbase, TCR2 has raised a total $173.3 million in capital, including an oversubscribed $125 million Series B financing completed in March 2018.

The Series B was co-led by 6 Dimensions Capital and Curative Ventures with participation from new investors including Redmile Group, ArrowMark Partners, Hillhouse Capital Group, MiraeAsset Financial Group, Syno Capital, Haitong International Securities, Lucion Group, Sirona Capital, Alexandria Venture Investments, and entities affiliated with Leerink Partners. They joined all of the company’s existing investors, MPM Capital (MPM BioVentures 2014 and UBS Oncology Impact Fund by MPM Capital), F2 Ventures, and Cathay Fortune Capital Investment.

“Off-the-shelf” TriTACs

Harpoon has developed Tri-specific T Cell-Activating Constructs or TriTACs, a novel class of T-cell therapeutics designed to achieve superior efficacy in penetrating solid tumors as an “off-the-shelf” T-cell therapy requiring less complex manufacturing than personalized or cell-based therapies.

TriTACs consist of three binding domains: A tumor target antibody, an HAS antibody, and a CD3 antibody. According to Harpoon, TriTACs offer several advantages over monoclonal antibodies besides less complex manufacturing requirements. These include an extended serum half-life allowing for convenient weekly dosing; a size about one-third that of a monoclonal antibody, expected to allow for faster diffusion into human solid tumor tissue; activity at lower levels of antigen expression; an ability to direct T cells to kill target cells independent of major histocompatibility complex (MHC) expression, which is expected to allow for more durable therapeutic responses than MHC-dependent approaches.

Harpoon said it planned to use net proceeds from its IPO to fund the clinical development of its prostate-specific membrane antigen (PSMA)-targeting TriTAC HPN424, indicated for prostate cancer; and its mesothelin (MSLN)-targeting TriTAC HPN536, being developed for ovarian cancer and other solid tumors.

The remaining net proceeds, Harpoon said, will be used to fund the development of its pipeline, including the B-cell maturation agent (BCMA)-targeting TriTAC HPN217, a DLL3-Targeting TriTAC, several ProTriTAC programs, and an unspecified number of discovery programs—as well as other general corporate purposes which according to the company may include the hiring of additional personnel, capital expenditures, and the costs of operating as a public company.

Metastatic Prostate Cancer Trial

In August, Harpoon said it treated its first patient in a Phase I trial (NCT03577028) designed to assess HPN424 in metastatic castration-resistant prostate cancer (mCRPC) patients. The multicenter, multinational, open-label, ascending dose study is designed to evaluate the safety, tolerability, and pharmacokinetics of HPN424 in approximately 40 patients with metastatic prostate cancer.

On December 2, Harpoon announced preclinical data supporting the development of HPN217, which is the company’s first TriTAC designed for the treatment of hematologic cancers, such as multiple myeloma.

Harpoon plans to trade its shares on the NASDAQ Global Select Market under the symbol “HARP.”

Harpoon’s registration statement disclosed a net loss of $17.635 million in the first nine months of 2018 versus $11.890 million for January–September 2017. For all of 2017, TCR2 reported a net loss of $16.830 million, compared with a net loss of $11.406 million in 2016.

Based in South San Francisco, CA, Harpoon closed in November on a $70 million Series C equity financing. OrbiMed served as lead new investor, along with new investors Cormorant, Ridgeback Capital Investments, Lilly Asia Ventures and NS Investment. Also participating were Harpoon’s existing investors MPM Capital, Oncology Impact Fund, Arix Bioscience, New Leaf Venture Partners, and Taiho Ventures.

Harpoon has raised a total $130 million in capital, according to Crunchbase.

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