Formed three years ago, privately held Medeor Therapeutics Inc. is moving its lead cellular immunotherapy candidate, MDR-101, directly into a pivotal phase III study, with its investigational new drug (IND) application cleared by the FDA along with agreement to a special protocol assessment (SPA).

The San Mateo, Calif.-based company is betting that one-time treatment with a product from its MDR-10X cell therapy platform, developed by researchers at Stanford University, will preserve or improve the function of transplanted kidneys – and, eventually, other organs – in both human leukocyte antigen (HLA)-matched and mismatched living donor transplants. Minimizing or eliminating the need for lifelong anti-rejection drug therapy could transform the kidney transplant experience for those patients.

Medeor raised a seed round in 2014 in conjunction with its formation, followed by a series A financing in 2015 – about $10 million, altogether, recounted Steven Deitcher, the company's co-founder, president and CEO. The six-person team then toiled on translating the scientific discoveries of Samuel Strober, professor of medicine and former chief of the division of immunology and rheumatology at Stanford's School of Medicine, into a commercial therapy. Strober, the company's scientific founder, also serves on the company's board.

The resemblance of the company's name to the common reference for a shooting star was no accident, Deitcher said, but the name also is the Latin word for "cure" – a notion the company takes seriously as it seeks to improve the long-term prognosis for organ transplant patients.

Medeor's strategy was to de-risk its platform before making a public splash, in part based on "the past challenges of other organizations in the cell therapy arena," Deitcher told BioWorld Today.

To wit, the company completed a transfer of the technology from Stanford, established contract commercial manufacturing capabilities and concluded its discussions with the FDA to garner the IND and SPA endorsements.

"These activities tell a very favorable story and set a very positive tone for the underlying technology, the capabilities of the company's management and the excellent prospects we have for the future," Deitcher said.

MDR-101 contains a formulation of organ donor-derived CD34+ hematopoietic stem and progenitor cells and CD3+ T cells, designed to induce mixed chimerism and persistent donor-specific immune tolerance in HLA-matched living donor kidney transplant recipients.

The prospective, randomized, open-label phase III study is expected to begin recruiting patients – the enrollment target remains under wraps – across 20 to 40 U.S. sites during the second half of 2017, according to Deitcher. The trial will evaluate efficacy and safety, with a primary endpoint of functional donor-specific immune tolerance – defined as freedom from immunosuppressants following completion of anti-rejection immunosuppressant drug therapy withdrawal – compared to control. Under terms of the SPA, a single successful pivotal study would lead to the submission of a biologics license application.

Deitcher declined to cite a timetable for the study's completion, noting that Medeor wants to preserve its options for additional meetings with the FDA under the SPA and, potentially, for an accelerated filing.

Once patients have been treated in the phase III, they'll be rolled into a long-term follow-up study, he added.

'ZERO CASES OF GRAFT-VS.-HOST DISEASE'

The Stanford team gained 10 years of clinical experience with the MDR-10X platform, including the conduct of phase I and early phase II trials, before it was in-licensed by Medeor, according to Deitcher. Those early studies showed that a single dose of MDR-101 produced hematologic mixed chimerism – the co-existence of recipient-derived and donor-derived blood and immune cells in the recipient – to support clonal deletion and immune regulation, which are the biologic mechanisms that underlie immune tolerance. By achieving mixed chimerism, MDR-101 is able essentially to reprogram a recipient's immune system to accept the donor kidney, inducing donor-specific immune tolerance and preventing transplant organ rejection.

Achieving mixed chimerism is, itself, a competitive difference from the complete chimerism of competing cell therapy approaches, but Medeor's technology offers two additional clinical advantages. The company doesn't need to use chemotherapeutics to condition patients. And its conditioning therapy, which consists of low-dose lymphoid irradiation, is not performed until organ transplant surgery is completed.

"These are key distinctions," Deitcher said. "The mixed chimerism underlies our mechanism of action, and we also feel strongly that mixed chimerism protects our patients from having a risk of any form of graft-vs.-host disease."

The claims are bold, since the approach, if proven, could revolutionize the transplant space. But Deitcher said the dossier of early findings on MDR-101 was sufficiently convincing to move the FDA.

"To date, in patients similar to the ones we'll be enrolling in our pivotal trial, the technology has been overwhelmingly successful, with zero cases of graft-vs.-host disease," he maintained. "The strength and compelling nature of the data generated at Stanford underpin the success that Medeor has had with our IND submission and SPA."

Although Strober also was a co-founder of now-defunct Dendreon Corp., a pioneer in cellular immunotherapy, no overlap exists between Medeor's and Dendreon's technologies, Deitcher added. Medeor holds an exclusive global license to its technologies and patents from Stanford and is pursuing additional patents under its own name.

Once the MDR-101 study is underway, Medeor plans to seek a larger series B, although no firm timetable or goal has been set for that round.

The MDR-10X technology platform also has the potential for use in other kidney transplant recipients. The company plans to advance a second candidate, MDR-102, into a phase IIb study in HLA-mismatched living donor kidney transplants. A third candidate, MDR-103, is in development as a one-time treatment for kidney recipient patients months or years post-transplant for whom immunosuppressant drug therapy is no longer effective and/or tolerable. Adding that indication could vastly expand the potential population of patients who could benefit from the company's therapy, Deitcher pointed out, including an estimated 50,000 previous kidney transplant recipients in the U.S. alone.

Medeor also is developing an equivalent program, known as MDR-20X, in the corresponding liver transplant patient populations.

In addition to Deitcher, who began his career as an academic researcher and executive before taking the reins of Talon Therapeutics Inc., Medeor's C-suite includes D. Scott Batty Jr., whose resume includes Sanofi SA unit Genzyme Corp. and Bristol-Myers Squibb Co., as chief medical officer; Elizabeth Read, formerly chief medical officer at Stemcyte and head of product development at Fate Therapeutics Inc., as senior vice president of product development; and Darin Weber, former executive vice president at Mesoblast Ltd., as senior vice president of regulatory affairs and quality.