CytoDyn’s PRO 140, a CCR5 antagonist called leronlimab, inhibited a human colon carcinoma cell line, SW480, metastases to liver and lung in a well-accepted mouse model in pre-clinical research phase. Cytodyn, a small emerging biotech, was recently cleared by the FDA for a Phase II protocol to proceed for combination therapy of their drug leronlimab and Regorafenib in patients with metastatic colorectal cancer (mCRC).
The Pre-clinical Research
The researchers implanted human colon carcinoma cells in the walls of immunodeficient mice and treated them with a control antibody or leronlimab. The small biotech company reports that after a month the mice were terminated and the lungs and livers were analyzed only to reveal statistically significant inhibition of metastases to lung and liver in the mouse model.
Supporting their Oncology Program
The recent pre-clinical study data supports the oncology program in place. The company seeks to capitalize on the FDA’s “Master Protocol” design option meant to expedite development of oncology drugs. This includes the use of “Basket Trial alternatives for single therapeutic agents with enrollment of different cancer histologic types when a single biomarker is identified,” reported the industry sponsor’s CEO Nader Pourhassan. He posits that in the case of CytoDyn “patients with metastatic disease of different histologic types, all expressing CCR5, will be enrolled.”
Basket trials involve a single investigational drug or drug combination that is studied across multiple cancer populations defined by disease stage, histology, number of prior therapies, genetic or other biomarkers, etc. Usually a single-arm, activity-estimating trial with overall response rate as the primary endpoint. So, for example, if a strong response signal is observed in a sub-study, the basket trial model could allow for an expansion of that study to generate data to support a marketing approval.
Hiring a Scientific Advisor to Accelerate Process
CytoDyn hired Bruce Patterson, MD, CEO of IncelDX, a science advisor, to help them “file for expanded access IND for patients with pancreatic, prostate, lung, breast, liver or melanoma cancers.” What is the rational? CytoDyn can “detect and qualify” the appropriate cell infiltrates establishing “leronlimab squarely in the personalized immune-oncology arena with a mechanism of action common to many tumors.”
What is Leronlimab?
An investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases and other diseases, including NASH, leronlimab has been granted “Fast Track” designation to the sponsor (CytoDyn) for two potential indications. The first is a combination therapy with highly active antiretroviral therapy (“HAART”) for HIV-infected patients, and the second is for metastatic triple-negative breast cancer. This investigational drug has been through nine clinical trials in over 800 people, including meeting endpoints in a pivotal Phase III trial according to its sponsor CytoDyn. They acquired their underlying intellectual property (e.g. PRO 140/leronlimab) via an acquisition of Progenics.
CytoDyn is a “micro-cap” publicly traded biotech trading at 31 cent per share as of this writing. They have little working capital and even faced shareholder lawsuit alleging that the company awarded excessive compensation (in form of stock options) to CEO Nader Z. Pourhassan. The lawsuit was settled. They lost about $56 million in 2019 and face a challenging road in securing sufficient capital for clinical research programs. They raised $14.5 million in private equity in 2013. Drug development entrepreneurs must be positive, persistent and creative to help this investigational therapy with seemingly good potential through to the next stages. For example they were able to secure a small business waiver of application fees by the FDA for the pending BLA filing for leronlimab as a combination therapy with HAART for HIV infected patients. Moreover, in the summer of 2019 they inked an arrangement with advisory IncelDX they hope will generate revenue from the license for the PA-14 antibody (diagnostic designation of the murine version of Pro140). In June, 2019 they raised $9.1 million from a completed public warrant tender offer. Combined with an additional $3 million raised from a private warrant exercise offer in May, new capital injected on a gross basis during June totaled $12 million representing 15 million shares of dilution. TrialSite News estimates CytoDyn employs between 10 to 20 staff.