Affinia has signed a multi-year agreement with CDMO Lonza to make gene therapy candidates targeting cancer and neurological disorders.

Swiss contract development manufacturing organization (CDMO) Lonza will provide manufacturing services for Affinia Therapeutics for two of its gene therapy candidates targeting metachromatic leukodystrophy (MLD), a rare neurodegenerative disease, and brain metastases secondary to human epidermal growth factor receptor 2 positive (HER2+) breast cancer.

Both candidates are based on the firm’s lead adeno-associated virus (AAV) vector, Anc80L65.

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Anc80L65-ARSA aims to treat MLD a genetic disease that results from the lack of functional arylsulfatase A (ARSA). The candidate has been designed to deliver the ARSA transgene via a one-time dose to the CNS through a lumbar puncture administration.

Anc80L65-trastuzumab, meanwhile, is being developed to treat HER2+ breast cancer.

While Trastuzumab is an approved monoclonal antibody (mAb) for the treatment of HER2+ breast cancer, Affinia claims the administration of this drug is impractical for achieving effective results and its candidate is designed to be administered as a one-time dose via lumber puncture.

While it has not been disclosed at which Lonza site the candidates will be made, the two companies already have an established relationship. The CDMO participated as a seed investor in Affinia’s Series A financing in March 2020 aimed at achieving a four-fold improvement in yield for Anc80L65.

According to the firm, Anc80L65 is 40 times more efficient at delivering genetic payloads to different parts of the brain than AAV9, a capsid used by different companies in the sector for central nervous system (CNS) gene therapies. However, for breast cancer, Affinia claims the levels of trastuzumab in the brain achieved by its gene therapy approach are up to 100 times higher than those achieved by current methods of administration.

While Affinia has internal pilot plant capacity and recently opened an office and lab in Waltham, Massachusetts, the partnership with Lonza has a mutual goal of securing flexible scaled-up manufacturing capacity over the next few years.

Three pillars

Both candidates form part of a pipeline based on Affinia’s Rationally-designed Therapeutics (ART) platform, which has been “created to address the key limitations of conventional gene therapies […] and consists of three pillars.”

The first pillar is novel capsids (cART), which are used to increase tissue targeting specificity, manufacturing, and immunologic profile. The second pillar is novel promoters (pART) used to control the expression of the therapeutic transgene in cell types. The third pillar is novel manufacturing approaches (mART), which the firm says improves yield, quality, and scalability across different product candidates

“Our platform enables us to engineer capsids that are more novel than existing technology (in terms of a higher degree of divergence from conventional AAV serotypes) while also retaining a high degree of functionality,” the spokesperson said.