Innate Pharma Confirms Securing Investment to Develop Novel ADC

The French biotechnology company Innate Pharma, which focuses on the discovery as well as the development and commercialization of novel therapeutic antibodies-based therapeutics to harness the immune system for the treatment of patients with various forms of cancer with significant unmet medical needs, has confirmed securing US $ 68.8 million, equivalent to approximately € 62.1 million to fund the development of antibody immunotherapies for solid tumors and blood cancer, including antibody-drug conjugates.* According to a report by Renaissance Capital, the funding included a US offering and a European private placement.

The aggregate gross proceeds of funding are before deduction of underwriting commissions and estimated expenses payable by the Innate Pharma.

Co-development
In late 2018 Innate Pharma and AstraZeneca signed multi-year collaborating agreement to accelerating each company’s oncology portfolio and bringing new medicines to patients. The collaboration enabled Innate Pharma to develop its commercial footprint and strengthened the company’s ability to invest in its immuno-oncology (IO) pipeline and R&D platform.

MabPlex
ADC Bio
Lonza
 

As part of the 2018 agreement, Innate Pharma in-licensed the US and EU commercial rights to AstraZeneca’s FDA-approved moxetumomab pasudotox-tdfk (Lumoxiti®) for the treatment of patients hairy cell leukemia. In turn, AstraZeneca obtained the full oncology rights to the first-in-class humanised anti-NKG2A antibody, monalizumab (previously known as IPH2201) humanized IgG4 targeting NKG2A receptors expressed on tumor infiltrating cytotoxic NK and CD8 T lymphocytes. The drug is co-developed in phase II with AstraZeneca for the treatment of head and neck cancer and colorectal cancer.

According to some financial experts, due to adverse market conditions in September and October, the fundraise was lower than the company’s target of US $ 79 million (€ 71.3 million). The company is expected spend a considerable amount of the secured funds to finance phase II trial of monalizumab and the clinical development of other cancer immunotherapies including a novel, site specific, antibody-drug conjugate or ADC.

Anti-MICA/B antibody-drug conjugate
In October 2018 AstraZeneca selected four molecules from Innate Pharma’s preclinical portfolio, including the anti-MICA/B antibody-drug conjugate IPH43 and the anti-Siglec 9 antibody programs. Two other programs are undisclosed and include a multi-specific NKp46 NK cell engager. Based on this selection, Innate Pharma elected to advance the anti-MICA/B program as an ADC-antibody and terminated the naked antibody (ADCC) program IPH4301.

The pyrrolobenzodiazepine (PBD)-based anti-MICA/B antibody-drug conjugate has a dual mechanism of action, including direct tumor cell killing and restoration of NKG2D-mediated immunosurveillance.

Based on their selective expression in a wide range of malignancies while, at the same time showing restricted expression in healthy tissues, MICA/B molecules are attractive targets for an ADC approach. Innate Pharma’s anti-MICA/B-PBD has demonstrated efficacy both in vitro and in vivo, paving the path for further evaluation towards clinical development.

In addition, both MICA and MICB serve as ligands forNKG2D, which is an activating receptor expressed on NK, CD8+T and γδ T cells. While the expression of MICA and MICB promotes recognition and elimination of tumors by these lymphocytes through NKG2D engagement, in vitro and in vivo studies have also reported NKG2D downregulation and lymphocyte dysfunction, leading to compromised immunity, als a result of chronic engagement of NKG2D by its ligands.

Mechanism of action of anti-MICA/B
Mechanism of action of anti-MICA/B. Image Courtesy Innate Pharma.

To solve this problem, scientists at Innate Pharma generated an ADC targeting MICA/B-expressing tumors with a dual function to achieve optimal therapeutic benefits, including killing of tumor cells while, at the same time, disrupting the interaction between MICA/B and NKG2D that induces impaired immunosurveillance. Initial results were presented during the 2018 annual meeting of the SITC. [1] IPH43 is currently in IND-enabling studies.

Adverse market conditions
The same adverse market conditions, which resulted in lowering European and US stock markets, may also have been a major factor of the withdrawal of ADC Therapeutics’ IPO and the poor performance shown by others (bio-) pharmaceutical companies.

Failed Phase II trial
In 2017 Innate Pharma’s drug candidate, a checkpoint inhibitor called lirilumab (IPH2102/BMS986015), failed in the phase II EffiKIR trial, a double-blind placebo-controlled randomized  study evaluating the efficacy in elderly patients with acute myeloid leukemia (AML). The trial, designed  to assess the efficacy of the candidate as a single-agent maintenance treatment in seniors whose AML was in first complete remission, did not meet the primary efficacy endpoint of leukemia-free survival.

Lirilumab was designed to block the interaction between KIR2DL-1,-2,-3 inhibitory receptors and their ligands, which facilitates activation of NK cells and, potentially some subsets of T-cells, ultimately leading to destruction of tumor cells.

Innate Pharma was originally founded in 1999. According to Nasdaq, the company booked US $ 143 million in collaboration and licensing revenue for the 12 months ending June 30, 2019.

Reference
[1] L’hospice F, Cornen S, Pouyet L, Morgado E, Remark R, Bregeon D, Montbel A, Anceriz N, et al. PBD-based anti-MICA/B antibody drug conjugate with a dual mechanism of action: direct tumor cell killing and restoration of NKG2D-mediated immunosurveillance. 33rd Annual Meeting of the Society for Immunotherapy of Cancer (SITC) 33rd. Poster 4 | SITC 2018 | Poster 4


*Based on an exchange rate of € 1 = US $ 1.1065 on October 16, 2019