During a 17-year stint at Novartis, Carolin Barth, MD, shepherded the development and launches of several antibody therapies that included two blockbuster drugs, Cosentyx® (secukinumab) and Xolair® (omalizumab).

Barth expects her commercialization background, and her earlier experience advising biopharma clients, to prove valuable in her new role as CEO of MiroBio, a two-year-old University of Oxford spinout specializing in developing precision immunology therapies.

MiroBio announced Barth’s appointment last week. Based at The Oxford Science Park in Oxford, U.K., MiroBio aims to advance therapies that address the immune imbalance that leads to autoimmune diseases. Those therapies—checkpoint agonist antibodies—are designed to precisely restore a balanced immune response and prevent the body from attacking its own cells, potentially providing durable remission from complex and often chronic immune-mediated conditions.

“A lot of people associate checkpoint inhibition or checkpoints in general with cancer therapy, because of PD-1s like [Merck & Co.’s] Keytruda® [pembrolizumab] and other therapies, and that makes total sense,” Barth told GEN Edge. “We’re using the knowledge that has been gained on checkpoint inhibition from the cancer therapies now to address the issues we’re seeing in autoimmune disease.”

Miro aims to capitalize on the role of checkpoint pathways as powerful regulators of immune cell function, with each pathway having its own role in specific types of immune cells and varying activity in disease. MiroBio uses a proprietary discovery engine, I-ReSToRE, to comprehensively map the 70+ inhibitory checkpoint receptor pathways, in order to identify therapeutic opportunities for autoimmune disease.

By selectively activating the right checkpoint receptors, MiroBio reasons, its therapies can deliver signals that are highly specific to cells and disease mechanisms, and potent enough to inhibit overactive immune cells without being too broadly immunosuppressive.

“When physicians treat patients with checkpoint inhibitors for kidney cancer, for example, what we quite frequently see as a side effect is that patients have autoimmune mediated disease, so they start to have, for example, inflammatory bowel disease or they demonstrate any other kind of autoimmune related disorder,” Barth said.

That compelled MiroBio to conclude that the checkpoint pathways not only play a role in cancer, but in autoimmune disease as well.

“The role they’re actually playing there is quite different than the one in cancer, that is, they are so toned down that they don’t really inhibit. They basically stopped having the autoimmune system in balance,” Barth said. “What we’re now going to do is basically activating the checkpoint receptors so that we’re restoring the balance that currently is not there.”

Clinic bound

Barth will oversee an all-preclinical pipeline whose two lead candidates are expected to advance into the clinic over the next couple of years.

MiroBio’s pipeline is led by MB272, a B- and T-lymphocyte attenuator (BTLA) agonist expected to begin clinical studies next year. MiroBio reasons that BTLA’s ability to modulate both B- and T-cells will give it a far-reaching regulatory effect and versatility as a target across several major autoimmune diseases.

MiroBio is not yet disclosing which autoimmune diseases MB272 or any of its other candidates will target. “What I can say is that we’re clearly going for the classic autoimmune diseases, where you have indications like IBD [inflammatory bowel disease] or rheumatoid arthritis or psoriasis,” says Barth. “It’s going to be in that space that we’re looking into.”

“We have had some really good interaction with academic centers, so we’re super interested in moving forward with this agonist,” Barth added. “Stay tuned: It’ll be public probably next year.”

The next furthest advanced candidate in MiroBio’s pipeline is MB151, a PD-1 agonist that the company is looking to advance into the clinic around the end of 2022 or early 2023.

MiroBio isn’t the only company looking a developing a PD-1 agonist in immunology: Eli Lilly’s pipeline includes LY3462817, a Phase II monoclonal antibody being studied for the treatment of rheumatoid arthritis and other autoimmune diseases, including psoriasis. LY3462817 is designed to suppress T-cell activation by binding to and agonizing the PD-1 inhibitory receptor.

Barth said MiroBio’s development of checkpoint agonists differs from Lilly on two key points.

“We don’t have just one agonist we’re pushing into the clinic,” she said, but multiple potential candidates through I-ReSToRE, which emerged from research and technology developed by the labs of Simon Davis, PhD, Professor of Molecular Immunology at the MRC Weatherall Institute of Molecular Medicine, and Richard Cornall, BM BCh, DPhil, Nuffield Professor of Clinical Medicine at the University of Oxford.

The platform’s analytics engine assesses:

  • Changes in receptor and gene expression as well as receptor signaling activity that occurs across immune cell types in immune-mediated diseases
  • How these changes affect in vitro and in vivo models of increasing complexity in healthy versus diseased states
  • The available capacity for modulation or “inhibitory reserve” in pathways of interest
  • The specific type of inhibitory receptor signaling with the greatest therapeutic potential in various patient populations

“We have functional proprietary assets that help us understand how do these receptors work on B cells, T cells, myeloid cells, so all the different cell types that are involved in the autoimmune system. And with knowing that part of it, we can really interrogate the different diseases to see, Okay, which checkpoint agonist is actually going to be best suited for which disease?”

Faster than planned

“We’ve got such exciting data on PD-1 that we’re actually advancing it much faster than the team actually a year ago had anticipated. I think in some ways, it’s going to be a bit of a head-to-head, the two going forward,” Barth said, referring to MB151 and Lilly’s candidate. “But I think that’s a good problem to have.”

It’s not the first time Barth has competed with Lilly, whose marketed drug Taltz® (ixekizumab) is, like Cosentyx, a human interleukin-17A antagonist with indications in forms of psoriasis and arthritis. Cosentyx, however, has the advantage in sales, having generated almost $4 billion last year compared with Taltz’s $1.79 billion. During the first half of this year, Cosentyx racked up $2.23 billion, more than double Taltz’s $972 million.

The second differentiator, Barth said, is MiroBio’s antibody engineering. While the company’s antibodies have Fc fragments and their respective receptors seen in conventional antibodies, MiroBio’s antibodies use a proprietary engineering design the company is not disclosing, for now.

“What we’ve seen—and that’s where we’re using also our own screening assays—is some nice preclinical evidence that they are really sophisticated monoclonal antibodies that we can modulate in the way they agonize the receptor,” she said.

Beyond MB272 and MB151, MiroBio has four preclinical candidates in earlier research phases with undisclosed mechanisms and indications. “They’re not yet in the stage where they would go into the clinic next year or the year after, but they’re progressing really nicely in terms of the early preclinical development right now,” Barth said.

Sustaining MiroBio’s development efforts is the £27 million (about $37 million) in Series A financing raised by the company in 2019, when it emerged from stealth. Oxford Sciences Innovation, an IP investment firm whose portfolio includes 100+ companies spun out of the University of Oxford, joined Samsara Biocapital to co-lead the round, joined by Advent Life Sciences and SR One.

“We are anticipating that we will initiate a Series B at some point next year,” Barth said.

She added that MiroBio was open to partnering with other biopharmas across its pipeline “to see whether we could then run maybe a pivotal program together or have them be the lead on it. I think that’s also where I bring quite a lot experience.”

From McKinsey to Novartis

After earning her MD and completing her residency at the University of Tübingen, Germany, Barth launched her biopharma career at McKinsey, where she focused on biopharma and healthcare clients as a junior engagement manager and senior associate.

She joined Novartis in 2004 as global brand leader overseeing pre-launch and launch activities for Lucentis® (ranibizumab), indicated for eye disorders that include wet age-related macular degeneration (AMD), diabetic retinopathy, diabetic macular edema, and macular edema following retinal vein occlusion. Barth moved into positions of growing responsibility, and served as global head for several development programs as well as a commercial launch leader in dermatology, rheumatology and chronic myeloid leukemia.

As global head of dermatology from 2013–16, Barth oversaw commercialization efforts for several dermatology compounds including Cosentyx and Xolair, with a focus on pre-launch/launch. Xolair—an anti-IgE antibody indicated for forms of asthma, nasal polyps and chronic spontaneous urticarial—generated $1.25 billion in 2020 sales and $690 million in the first half of 2021.

Most recently as global head of commercial and pipeline strategy, cell and gene, at Novartis Oncology, Barth led a cross-divisional and cross-functional pipeline strategy team in defining strategy and priorities for all Novartis cell and gene pipeline activities across research, development, manufacturing and commercialization.

In July, Barth was among 25 women biopharma executives selected by Executive Women In Bio, an initiative of Women In Bio, to participate in the 2021 Boardroom Ready Cohort, an executive development platform designed to promote greater participation by women on corporate boards.

Barth is the latest and highest senior executive to be appointed by MiroBio in recent months. CFO Julian Hirst, MBA, joined the company from Immunocore where, as corporate finance director and head of investor relations, he played a key role in that company raising more than $930 million in three private rounds, a venture debt financing and an IPO.

Lynne Murray, PhD, MBA, has been named MiroBio’s Senior Vice President, Research and Development after previously serving as head of regeneration, early respiratory and immunology at AstraZeneca. She was formerly head of fibrosis biology at AZ-acquired MedImmune, where she established a fibrosis pipeline that delivered multiple assets into the clinic.

“She’s really built up our research and development team and has been instrumental in moving those two compounds that we’re now our lead candidates forward,” Barth said of Murray. “She has been instrumental as well in building and putting in a very good structure around antibody engineering, as well as a further profiling of the I-ReSToRE platform.”

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