MedImmune Looking For Multi-Purpose Biologics For Metabolic Diseases

Moving over from the academic world, Christopher Rhodes plans to help revamp MedImmune LLC’s cardiovascular and metabolic disease discovery and research work, with a goal of finding and validating mechanisms to address early occurrences that can lead to diabetes and obesity.

Rhodes joined the Maryland-based biologics arm of AstraZeneca PLC in July from the University of Chicago, where he was research director at the Kovler Diabetes Center as well as a professor of endocrinology and chair of a committee on molecular metabolism and nutrition. Chicago was the latest stop in an academic career that also included Harvard Medical School, University of Cambridge and the Joslin Diabetes Center, but Rhodes said he should not be seen simply as an academic switching sides to private industry.

Before completing his doctorate studies, Rhodes worked in veterinary medicine at Beecham Pharmaceuticals, now part of GlaxoSmithKline PLC. But his work in academic settings often straddled the public/private divide, he said in an interview.

“For me, [the transition is] not necessarily a challenge because I’ve been involved during my academic life in consulting and on a few occasions partnering with industry for many years, and I’ve also been a proponent of what real translational medicine is,” Rhodes explained. “I think it’s very hard to do in the academic world. A lot of academics think that they can discover something and create a biotech company that will develop it on its own, and they forget that it’s going to cost in excess of a billion dollars in this day and age to actually get [that discovery] to the bedside.”

An Area To Revamp

Although the MedImmune/AstraZeneca pipeline is somewhat sparse in the cardiovascular and metabolic fields, Rhodes called his mission less a rebuild than a revamp.

MedImmune boasts three Phase I candidates in the area: MEDI0382, a GLP-1/glucagon dual agonist for diabetes and obesity; MEDI6012, an LCAT candidate for acute coronary syndrome; and MEDI8111, an Rh-Factor II candidate for trauma and bleeding. AstraZeneca has roxadustat, a hypoxia inducible factor prolyl hydroxylase inhibitor in Phase III for anemia related to end-stage renal disease or chronic kidney disease; tenapanor, an NHE3 inhibitor in Phase II for ESRD and CKD; and ASZ4901, an NK3 receptor antagonist in Phase II for polycystic ovarian syndrome.

Rhodes said the pipeline is building up, particularly in the biologics realm, “which is a really exciting direction to go in the metabolic disease field.” MedImmune’s technological capabilities could lead to candidates that address more than one of the co-morbidities related to metabolic disease, he added. While focused on MedImmune’s work and biologics specifically, Rhodes said his new role also will require him to “build complementary bridges with the AstraZeneca operation.”

A top research priority will be looking into new ways to tackle the outcomes of metabolic syndrome and fatty liver disease, he said, which has implications across the spectrum of diabetes, obesity, cardiovascular disease, renal disease and fatty liver disease.

“We’ll try and find a therapy that addresses many of the multiple symptoms that go along with diabetes and obesity with one therapeutic,” Rhodes said. “For example, in type 2 diabetes, you have insulin resistance which can be driven by a fatty liver, or by being overweight or obese. This leads to an insulin-insufficient state, where the patient loses the cells that make insulin. So, if we can alleviate the fatty liver and the insulin-resistance part of it, we’re addressing comorbidities all in one, and it’s possible that the beta cells might fix themselves if you get a molecule that can improve insulin sensitivity.”

“In the past, people have looked for compounds just to fix insulin resistance; now, I think we’re looking for compounds that will address insulin resistance, clear a fatty liver, make people lose weight, improve beta cell function, even lower the chronic inflammation,” he continued. “We’re looking for one stone to kill many birds in disease at the moment, and I think the agencies that approve these products will be very encouraging of that, as well.”

Rhodes indicated that MedImmune has “nice tricks up our sleeves” in terms of new plans or approaches to addressing issues such as non-alcoholic fatty liver disease, but added that specifics probably won’t be disclosed for another year or so. “We need to address the issues that are occurring early on in the pathogenesis of the disease to prevent the cascade of events that happen downstream of that,” he said.

Partnering More Closely With Academic Researchers

Given his background in academia, Rhodes likely can be relied upon to seek opportunities for external innovation, something he said would be vital not just to MedImmune’s prospects, but to academic-sector research outfits in an era of NIH research funding limitations. He said he would seek out partnerships in which MedImmune and academic researchers would work more closely than typically seen in private/public partnerships.

“For example, an academic lab might discover a potential target and that might be of interest to a commercial entity to develop and see if they can actually target it,” he explained. “So, the commercial side might work on a drug while at the same time the academic lab is actually substantiating the mechanisms and biochemistry and physiology behind that mode of action for a therapy, so they can work hand in hand and complement each other’s research.”

MedImmune has signed two partnerships in the metabolic space since 2013, including one this past March with Joslin Diabetes Center, where Rhodes once worked, to identify new drug candidates based on three initial projects: protecting and regenerating insulin-producing beta cells; increasing the caloric utilization of fat depots; and replicating, pharmacologically, the beneficial effects of bariatric surgery [See Deal]. In 2013, the company partnered with NGM Biopharmaceuticals Inc. to discover and develop new candidates for diabetes and obesity based on the biotech’s enteroendocrine cell platform [See Deal].

On the job just a few weeks at the time of his interview, Rhodes said his early focus has been on evaluating the ongoing science within MedImmune’s cardio-metabolic apparatus to determine which discovery and preclinical projects should be prioritized. He’ll play a role in making decisions on the clinical development pipeline, but his focus will be on work leading up to the IND stage.