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Novartis highlights 4 drugs of future in laying out R&D vision

As Vas Narasimhan nears the two-year mark as Novartis’ chief executive, his impact on the Swiss pharma has already been evident, as shown Thursday at the company’s R&D day.

Narasimhan has reshaped large portions of the business to focus on higher-margin pharmaceuticals. That’s meant shedding its consumer healthcare presence and eye-care unit, while pulling the trigger on multibillion-dollar acquisitions in gene therapy, radiopharmaceuticals and, most recently, for an RNA interference-based drug.

While those external acquisitions have been headline-grabbing moments, the R&D day presentation — spanning more than three hours and 180 slides — also showed incremental progress in Novartis’ own labs.

Among Phase 2 assets, for instance, an internal company analysis found 92% of those drugs are expected to be either first-in-class or first-in-indication, as the Swiss pharma discontinued many assets that don’t meet that bar.

And M&A isn’t the only area Novartis is gambling in, as company executives outlined ambitious development plans for a select group of drugs out of its 164 assets in clinical testing.

In particular, the pharma highlighted four emerging experimental therapies. These aren’t as well-known as the Novartis’ current growth drivers or late-stage pipeline, but company executives frame them as key parts of Novartis’ future, with all expected to soon enter pivotal testing.

​1. iscalimab

Novartis billed this monoclonal antibody that blocks the CD154-40 pathway as potentially providing “one transplant for life,” hoping the drug can become the new standard of care in transplants.

Eric Hughes, global development head for immunology, hepatology and dermatology, compared the therapy’s potential impact on the transplant space to cyclosporin’s 35 years ago.

In the presentation, Hughes said there remains room for significant improvement with transplants, saying that less than half of transplanted kidneys are functional after a decade. The hope is iscalimab can lengthen those timelines and reduce side effects.

Iscalimab is also being tested in Sjogren’s syndrome, a common autoimmune disease marked by dry eye, dry mouth and severe fatigue levels. Phase 2b studies in both kidney transplant and Sjogren’s are expected to read out in 2021, and those are two of six indications currently being tested.

2. LNP023

On Thursday, Novartis shared the first glimpse of clinical data for LNP023 in paroxysmal nocturnal hemoglobinuria, a rare blood disease known as PNH.

Cantor Fitzgerald analyst Eliana Merle estimated the early results appeared to be from 16 to 18 patients, testing LNP023 as a monotherapy and in combination. Results showed evidence of activity in lowering levels of a key enzyme in PNH known as LDH, Merle wrote in a research note to investors.

The Swiss pharma has plans to simultaneously test LNP023, a Factor B inhibitor targeting the alternative complement pathway, in IgA nephropathy, membranous nephropathy and C3 glomerulopathy.

3. MBG453

MBG453 is an anti-TIM-3 monoclonal antibody in a pivotal Phase 2 trial for myelodysplastic syndrome. Phase 1 data from the MDS program will be presented at the American Society of Hematology’s upcoming annual conference this weekend.

Novartis hopes MBG453 will become the first therapy to reach market that targets TIM-3, which is selectively expressed in leukemic stem cells.

The company says it is the sole TIM-3 antibody being tested in MDS and acute myeloid leukemia. Phase 2 AML studies are expected to kick off in the first half of 2020.

The pivotal MDS program is expected to lead to MBG453’s first regulatory submission in 2021.

4. TQJ230

Stemming from a collaboration with Akcea Therapeutics, TQJ230 is an antisense oligonucleotide aiming to reduce lipoprotein(a) levels, a risk factor for cardiovascular disease.

The drug would further expand Novartis’ ambitions in the cardiovascular space, which were just significantly bolstered by the nearly $10 billion acquisition of The Medicines Company and another RNA-targeting heart drug in inclisiran.

In February, Novartis exercised the rights on the deal with Akcea to take over development and commercialization on TQJ230. That includes running a large cardiovascular outcomes study, in which the company plans to begin enrolling 7,500 patients starting next year.

Narasimhan said Thrusday that trial will be powered to target a cardiovascular risk reduction of roughly 20% to 25%.