After failing to transition its cancer portfolio from chemotherapy to targeted cancer drugs, Sanofi is recharging its cancer strategy, relying on a collaboration with Regeneron Pharmaceuticals Inc. to vault it into the hot field of immuno-oncology.

“For a variety of reasons we didn’t perform in a way that we would have wanted to,” Nabel said. “That caused us to step back, to do the reorganization with a little bit of restructuring and now take off with more focus, more resources, more resolve to be successful in immuno-oncology.”

Betting that Sanofi can come from behind to become a leader in oncology sounds like a high stakes wager given the company’s past missteps and limited late-stage pipeline, but Sanofi seems to have realistic expectations of the challenges.

“We recognize it may take a while for us to become leaders in oncology, but there is certainly a lot of room for us to become respectable participants in oncology,” Chief Scientific Officer Gary Nabel said in an interview.

Considering the steep projections for growth in the cancer drug market, he added, “if we can just be part of that growth we will be happy.”

Certainly, Merck & Co. Inc. has shown with the launch of the first programmed cell death-1 (PD-1) inhibitor Keytruda (pembrolizumab) that a company with little experience in cancer R&D can establish a successful oncology franchise – as long as it has a golden nugget in its arsenal.

Sanofi, to its credit, has a long history in oncology, having sold the chemotherapies Taxotere (docetaxel) and Eloxatin (oxaliplatin) before they went generic. Taxotere, a blockbuster seller, lost generic exclusivity in November 2010, and the company never really regained its footing in the field.

New launches like the next-generation chemotherapy Jevtana (cabazitaxel) and the vascular endothelial growth factor 2 (VEGF 2) inhibitor Zaltrap (ziv-aflibercept) have failed to deliver substantial revenues to the top line for various reasons, including toxicity with Jevtana and tough competition and a pricing scandal associated with the launch of Zaltrap Also see "Role Of Cost And Evidence In Value-Based Purchasing Highlighted By Zaltrap Price Adjustment" - Pink Sheet, 24 December, 2012..

Sanofi nonetheless generated €1.4 billion ($1.53 billion) in oncology sales in 2014, with Jevtana being the top-seller – barely outpacing Taxotere – with €273 million in sales.

Taking A Step Back To Reset

In a big setback to Sanofi’s ambitions in oncology, the company experienced two high-profile late-stage development failures in 2013: the PARP inhibitor iniparib for breast and lung cancer and the Janus kinase 2 (JAK2) inhibitor fedratinib for myelofibrosis Also see "The Bell Tolls For Fedratinib In A Setback For Sanofi’s Oncology Portfolio" - Pink Sheet, 18 November, 2013..

Following those disappointments, the company took a step back in 2014 to reevaluate its strategy. It reduced the size of its oncology research group a bit as a result, by less than 10%, according to Nabel.

The company also went through a top level management shakeup with CEO Christopher Viehbacher being pushed out by the board of directors last year and eventually replaced in April with former Bayer HealthCare LLC CEO Olivier Brandicourt ([A#14150219005]).

Around the same time, the company’s head of global oncology Tal Zaks left the company and took the job of chief medical officer at Moderna Therapeutics LLC.

“For a variety of reasons we didn’t perform in a way that we would have wanted to,” Nabel said. “That caused us to step back, to do the reorganization with a little bit of restructuring and now take off with more focus, more resources, more resolve to be successful in immuno-oncology.”

The company has been one of the last big pharmas to jump into the immuno-oncology space, but it hopes the ace in its deck will be Regeneron, the fast-growing biotech that has been its long-time collaborator.

Under a new alliance, announced July 28, the companies agreed to collaborate on the discovery, development and commercialization of new antibody cancer treatments in immuno-oncology, including a PD-1 inhibitor in Phase I.

The candidates will come from Regeneron’s labs, and in exchange, Sanofi will make an upfront payment to Regeneron of $640 million. The companies will invest $1 billion for discovery through proof-of-concept (usually Phase IIa) of monotherapy and combinations, of which Sanofi will fund 75%.

The companies also agreed to equally fund an additional $650 million evenly split for development of the PD-1 inhibitor, REGN2810, and reallocated $75 million over three years for immuno-oncology from Sanofi’s $160 million annual contribution under the existing antibody collaboration. Additional funding will be allocated as programs move beyond proof-of-concept.

But Nabel noted that the companies have been moving toward this deal for some time, under their original collaboration.

“This work has been ongoing with the existing Regeneron agreement for three or more years. There is a whole set of assets that have grown from that collaboration,” he said.

Sanofi’s longstanding deal with Regeneron has been fruitful, delivering most recently the first PCSK9 inhibitor to reach the US market, Praluent (alirocumab), expected to become a blockbuster ([A#14150724005]).

The two have been partners since 2003, when Sanofi (then Aventis) took a stake in Regeneron and paid $510 million for rights to aflibercept for cancer, now on the market for colorectal cancer as Zaltrap. Regeneron separately and independently developed aflibercept for ophthalmic indications, which is now on the market as Eylea and considered one of the best drug launches in recent history.

The two partners doubled down on their partnership in 2007, with Sanofi paying $85 million upfront and $475 million in R&D funding over five years plus additional milestones to develop other antibody drugs, including two that are now in late-stage development [See Deal].

“The teams know one another. They complement one another in terms of their various strengths,” Nabel said. “Regeneron is very good at antibody discovery in terms of early research. Sanofi is very good on the translational and development as well as the commercial side of distributing new medicines. Together I think we both can do things that neither one of us can do alone.

Behind, But Jumping Into Combinations

The challenge in immuno-oncology will be catching up to the leaders in the field – companies like Merck and Bristol-Myers Squibb Co., both with immune checkpoint inhibitors already on the market and others like Roche, AstraZeneca PLC and even Pfizer Inc., which have broad pipelines and drugs further advanced in development – and determining the most effective combinations.

“Admittedly, we weren’t there on the first wave,” Nabel acknowledged. “We really view this as the beginning of a long race. The enemy here is cancer.”

“It’s really looking at the big picture of what lies ahead, what assets we have individually, but more importantly what we have together that convinces us it’s a good place to work together and advance the field,” Nabel said.

Given the companies’ come-from-behind position in the development race, they don’t have enormous expectations for their PD-1 inhibitor as a monotherapy. Bristol’s Opdivo (nivolumab) and Merck’s Keytruda (pembrolizumab) are already on the market and others, including PD-L1 inhibitors, are expected to reach the market in the next few years.

“We see the real upside for PD-1 as being in the combinations,” Nabel said, since the drugs are considered to be one of the cornerstones of immuno-oncology treatment.

The next targets Sanofi and Regeneron will pursue are lymphocyte-activation gene 3 (LAG3), glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and PD-L1. All are currently in preclinical development, but the companies said they hope to begin testing new targets in the clinic in 2016.

Sanofi will also continue to advance its own independent oncology pipeline, including some early immuno-oncology programs that could be added to the alliance at a future date or be developed by Sanofi.

The company’s most promising mid-stage oncology program is an anti-CD38 antibody, isatuximab, in Phase II development for multiple myeloma. Another program highlighted by Nabel is a transforming growth factor (TGF) beta antibody, discovered at Sanofi’s Genzyme unit and initially studied for fibrosis. But TGF beta is a potent immuno-modulator in immune response in cancer, so the company plans to explore that further as well.

The company may bring in new assets and technologies as well, and can fold them into the collaboration with Regeneron under the current deal structure, which requires either company to offer any promising external assets to the alliance first before pursuing development independently.

The deal with Regeneron represents something of a fresh start for Sanofi in oncology. The road to reclaiming a strong position in the space will be long, but at least now the company appears to have found a path forward.

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