Oncology

Oncology research has attained priority status and has been flush with pharma research dollars for years. Drug development companies raised $7 billion in 2020 due to the disease’s heavy human toll, and cancer drug sales may nearly double to $320.6 billion by 2026. 

It’s no surprise then that three types of cancer — breast, solid tumors and prostate — made the top five list of most studied diseases in 2023, according to the Phesi Global Analysis report, which looked at more than 65,000 trials involving 100 million patients. Breast cancer, which topped the Phesi list for the third year in a row, is one of the two most common cancers globally and accounts for one in every three cancers in American women. A 2023 report from PhRMA found that there are currently 94 drugs in the pipeline for breast cancer. While the death rate for the disease dropped 43% from its peak in 1989 to 2020, there is still demand for more effective treatments for metastatic cancers and more aggressive types of cancer, such as triple negative disease, and those that express the HER3 protein, which have no approved treatments, according to PhRMA.

In addition to breast cancer, research into solid tumors and prostate cancer also made Phesi’s top five, coming in at number two and five respectively.  

“The positive news is there has been an increase in trial recruitment across all the top five indications in 2023,” said Dr. Gen Li, Phesi’s president. “What has been especially notable is the increase in solid tumor trials. These are likely to be the foundation of innovative cancer therapies, and investment in this area is a promising sign for patients.” 

Solid tumors have gained more attention in recent years, and 677 medicines are in development to treat them, according to PhRMA. An additional 78 medicines are in the works for prostate cancer, the most common in U.S. men.

The other two of the top five most studied disease spots last year went to COVID-19 and stroke research. Not surprisingly, trials for COVID lost steam through the year as the sense of urgency related to the disease dwindled and the public tried to put the pandemic behind it. 

“We have seen a marked reduction in investment into COVID therapies in 2023, likely due to there being fewer available patients,” Li said. “The prospective market for COVID therapies is less attractive for investment, and we expect this downward trend to continue.”

However, investments in stroke R&D jumped three spots from fifth in 2022 to second in 2023. The number of stroke-related deaths, particularly in younger people, is expected to double by 2050, which may be fueling interest in this area.

Overall clinical trial activity was also scaled back in the wake of the pandemic. Phase 2 trial attrition was down 1% since 2022, but still hovered at 28%, marking a sizable jump from the 20% attrition rate seen before the pandemic, according to Phesi. 

“Ultimately, the clinical development industry is beginning to recover from the pandemic, but we can expect the long-term impact to stretch into 2025,” Li said.  

This could slow the pace of new drugs coming to market and may put further pressure on future R&D costs.

Initial public offerings in biotech have appeared to be on the upswing in the first two months of the year, with a handful of launches reaching over $100 million. The offerings brought back some excitement after a few tough years marked by the rising cost of capital due to higher interest rates, other macroeconomic headwinds, a sluggish investment environment and fewer IPOs than during the pandemic.

The strong start has been hailed as a possible rebound for the industry, but it’s not quite time to celebrate, according to David Crean, managing partner of M&A and strategic advisory firm Cardiff Advisory. 

“It's a good start to the 2024 IPO class, but I think there needs to be a little bit more energy and momentum going into [the market],” Crean said. “It's not a switch you're going to just turn on.”

Instead of a flood of biotech IPOs in 2024, there may be a steady stream through 2025 as economic conditions improve and the market becomes more favorable. Looking at the performance of some of the companies that have launched in the first two months of the year is a good indicator of which biotech areas are now ripe for IPO success.

Top biotech IPO target areas

Companies that reaped millions in fundraising during the pandemic years when investors were “spending like drunken sailors”  due to historically low interest rates, may be readying for an IPO in the near future, Crean said. The sector’s troubles, defined in part by rising layoffs last year, may be symptomatic of a spending hangover rather than an ongoing challenge for the entire sector. 

And for those readying an IPO, the move may be to “survive to 2025,” according to Crean, who predicts more IPO announcements in the next 15 to 18 months. Interest rates could also fall in the coming months, which could rally the sector. 

The fundamentals that make for a good IPO candidate in biotech are largely derisked companies with late-stage therapies, according to Crean, although early-stage companies will still sometimes go public.

“For very early stage companies that are looking to go public, it represents some challenges,” Crean said. “As a public market investor, they'll want to see high-quality clinical candidates from drug development companies being prioritized over the earlier states that exit the risks.”

Beyond those fundamentals, investors are eyeing specific areas within biotech, including oncology, autoimmune and cardio metabolic disease. And 2024 biotech IPOs in these areas have already seen success. 

CG Oncology, the sector’s first IPO of 2024, initially raised a larger-than-expected sum of $380 million in its public offering and has since seen its stock rise further. The company, which is focused on developing therapeutics for patients with bladder cancer, launched its IPO at $19 per share and is currently trading around $35 per share as of market close March 12. The success of its launch and subsequent value growth makes the company one to watch, according to Crean, who pointed to the oncology focus and late-stage candidates as possible triggers for future IPOs.

Cardio metabolic disease and “anything to do with diabesity” — diabetes and obesity, said Crean — are other areas likely to see more IPOs. The success of Novo Nordisk’s Wegovy and Ozempic and Eli Lilly’s Mounjaro are indicators of investors’ appetite in the space. 

Crean also clocked autoimmune as a top target, and pointed to Kyverna Therapeutics, which launched an IPO in February that raised $319 million. The developer of cell therapies for autoimmune diseases launched its IPO with shares priced $22 a piece and is now trading around $29 per share as of market close March 12.

Biotechs to watch

While 2024 started off with a bang, a surge of IPOs could still be coming this year and into 2025.

“I don't anticipate a broadening of the big IPO market until maybe the second half of this year,” Crean said.

Recent moves by high-profile investors, the timing of the latest funding round and the financial momentum in the industry’s subsectors are all key factors when predicting potential biotech IPO candidates. With these fundamentals in place, some biotechs may be ready to pounce on improving market conditions. Here are some of the biotechs to watch for a potential IPO and some that have already announced their intended offering, according to Crean.

Boundless Bio: Precision oncology startup Boundless Bio recently announced its planned IPO, and the company has a strong cap table of “significant investors” behind it, including Bayer, RA Capital, Vertex Ventures HC and more. The early-stage biotech’s pipeline is focused on ecDNA-driven cancers. 

Alumis: Fresh off a series C funding round that brought in $259 million, Alumis is a clinical-stage biopharma company developing oral therapies for autoimmune diseases. The company plans to use the financing to initiate pivotal phase 3 clinical trials for its lead TYK2 candidate, ESK-001, which treats moderate to severe plaque psoriasis. The company has called its candidate “best in class,” and if approved, the drug would compete with Bristol Myers Squibb’s psoriasis pill Sotyktu, which scored an FDA nod in 2022. With recent funding, it’s unlikely Alumis will seek an IPO in 2024, but it could go public in 2025 or beyond, according to Crean.

Endeavor BioMedicines: With $163 million in funding already raised, California-based Endeavor Therapeutics’ pipeline includes two candidates for idiopathic pulmonary fibrosis. The company also penned a licensing agreement with Hummingbird Bioscience last year for exclusive rights to HMBD-501, a next-generation HER3-targeted ADC. With the company’s last fundraising round in 2022, it could be looking to raise capital through an IPO next. 

Autobahn Therapeutics: San Diego-based Autobahn Therapeutics develops regenerative medicines aimed at CNS disorders. Its early-stage pipeline includes small molecule therapies for both rare and prevalent CNS disorders, while its lead molecule, a CNS-directed thyroid hormone receptor beta (TRβ) agonist, is initially targeting major depressive disorder. Autobahn has raised nearly $109 million and counts Biogen, Pfizer Ventures and BMS among its major investors.

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Colorectal cancer screening works. Yet, not everyone who needs screening gets it.

“The biggest epidemic, the biggest challenge we have for colorectal cancer is the unscreened population,” said Helmy Eltoukhy, co-CEO and chairman of Guardant Health, a California-based precision oncology company. “There are 50,000 Americans that die every year from colorectal cancer, and 76% of those deaths come from the unscreened population.”

It’s an issue that recently grabbed headlines when new research showed colorectal cancer deaths are rising among younger patients, and that colorectal cancer is now the leading cause of cancer death in men and the second-leading in women younger than 50. Although screening is effective, colorectal screening methods, like colonoscopies and stool sample testing, don’t always have the best compliance. According to the CDC, a statewide average of 69.4% of U.S. adults aged 50 to 75 weren’t up to date with colorectal cancer screening in 2020. 

“If we had a blood-based methodology to screen those unscreened individuals, it would probably, from our estimate, be one of the most significant advances in cancer mortality, at least in the last decade,” Eltoukhy said.

With that goal in mind, Guardant Health created Shield, a blood-based test that can detect colorectal cancer with 83% sensitivity through tumor DNA, according to a 20,000-patient study. It’s already on the market with a CLIA certification, but the company is also seeking FDA approval and is in the final stages of FDA review, Eltoukhy said.

“We expect that FDA decision, and hopefully approval, to come sometime this year, and if it does, it would be the first FDA-approved, Medicare-reimbursed sort of ‘liquid biopsy’ for screening ever,” Eltoukhy said.

The impact for pharma research

Guardant has two other Medicare-reimbursed blood-based cancer tests already on the market: Guardant Reveal, a companion tool which detects residual disease and recurrence in current early-stage colorectal, breast and lung cancer patients, and Guardant360, which can help doctors match advanced cancer patients with the right treatments and monitor their response.

Biotech companies also use Guardant360 for finding clinical trial candidates and validating drugs.

“If you could remove the friction in terms of finding patients because you can do things with blood rather than biopsies [or] other more involved medical procedures, it really reduces the time to enrollment,” Eltoukhy said. “We’ve seen a lot of success stories as a result.”

In addition, Eltoukhy said the drug validation capabilities have been useful for companies reevaluating their pipelines to ensure drug candidates have large enough indications in the face of Medicare price negotiations down the road.

“The fact that they’re thinking about the larger indications means they often have to measure twice and cut once,” he said. 

Guardant’s Shield is initially indicated for colorectal cancer, but that’s a “Trojan horse strategy” to test for other cancers, too.  

“The same test will be able to do dozens of other cancers. We have a 10,000-plus patient study that is enrolling very nicely in lung cancer,” Eltoukhy said. “Data rich blood tests, which have never really been part of the medical space, will start coming to bear with colorectal. But I think from there, all that data that’s unlocked will be so useful for many other applications over time.”

Pharma companies are also exploring ways to use the technology in other disease areas, such as inflammatory disease, rheumatoid arthritis and cardiovascular disease. He expects some of that work to be announced later this year.

“This is … the first breakthrough that is leading to what we all envisioned personalized medicine and precision medicine to enable,” Eltoukhy said. “We’re finally seeing that promise.”

Welcome Biotech Spotlight, a series featuring companies that are creating breakthrough technologies and products. We’re looking at Black Diamond Therapeutics, which is developing oral treatments targeting a broad swath of mutations in lung and brain cancers.

In focus with: Dr. Mark Velleca, CEO and chairman of the board of Black Diamond Therapeutics. 

Black Diamond Therapeutics’ vision: Cancer is destructive and wily — deftly mutating to outwit effective treatments. To help overcome this challenge, Black Diamond is developing oral therapeutics that target mutated types of non-small cell lung cancer (NSCLC) and glioblastoma, an aggressive brain cancer.

Why it matters: Patients with mutated cancers often have few treatment options. Those that do exist can bring challenging side effects. 

Black Diamond’s oral therapies have shown promise in treating tumors with cancer-driving mutations and are easier for patients to take, Velleca said.

The company’s pipeline: Black Diamond’s most advanced treatment, BDTX-1535, is in phase 2 for NSCLC and targets three groups of epidermal growth factor receptor (EGFR) mutations that can either arise with the tumor or develop in response to treatment with drugs like AstraZeneca’s blockbuster Tagrisso, which itself targets mutations driven by earlier inhibitors like Tarceva. 

EGFR mutations are present in 20% to 50% of NSCLC, the most common type of lung cancer. 

“BDTX-1535 is unique in that it hits the two big driver classical mutations, it hits all of these non-classical mutations, and it hits this new resistance mutation, C797S,” Velleca said. The C797S mutation is one that arose in response to Tagrisso. “[BDTX-1535] is the only drug that hits all three of those classes,” Velleca said.

In a phase 1 NSCLC trial, five of 13 patients with three mutated tumor types saw their tumors shrink by at least 30% when taking the once-daily oral treatment. The treatment appeared to stop tumor growth in seven other patients, and there was evidence that it reduced brain metastases. 

The company also saw favorable results in a phase 1 of BDTX-1535 for glioblastoma trial, which can also be driven by EGFR mutations. 

Another molecule Black Diamond has in the works is BDTX-4933, designed to inhibit class I, II and III RAF/RAS-mutant tumors. It’s now in phase 1 for KRAS-mutant NSCLC and RAF/RAS-mutant solid tumors. The company also has two preclinical-stage prospects.

The road to approval: Now, the goal is to get BDTX-1535 to market as quickly as possible to benefit patients, Velleca said. The company isn’t divulging its regulatory strategy, but if all goes well the drug could move into phase 3 in 2025, and hit the market in 2027. While there have been questions about Black Diamond’s rapid cash burn rate, the company has been reining in its spending to ensure it has enough steam to carry it through its projected 2024 milestones and into 2025.

Velleca said the company thinks BDTX-1535 can distinguish itself in a crowded NSCLC field because patients and doctors typically find once-daily oral treatments appealing. 

“Many of the newer therapies are antibody drug conjugates, which come with infusions every three weeks and lots of associated side effects,” Velleca said. “They’re not tethered to an IV pole.” 

BDTX-1535 could also find a place in multiple treatment stages. 

“We think there's an opportunity to benefit patients with this drug across all lines of therapy — front line, second line, third line,” Velleca said. 

Among the possibilities is providing a new option for patients whose cancers are no longer held in check by Tagrisso. 

“Where we're going to go first for registration, we have not disclosed yet. We’ll certainly let the data drive us there,” Velleca said.

A long development road has paid off for Iovance Biotherapeutics, which recently won an accelerated approval for the first cell therapy to treat advanced melanoma. The FDA OK will also swing the door open to a promising type of immunotherapy for solid tumors. 

Iovance’s Amtagvi uses tumor-infiltrating lymphocytes (TIL) immune cells taken directly from the tumor and fortifies them to fight cancer. 

Academic researchers have studied TIL therapy for decades, but scientific and regulatory factors slowed the path to commercialization, said Jason Bock, co-founder and CEO of the Cell Therapy Manufacturing Center (CTMC), and an expert on TIL therapy. 

“This is the first cell therapy modality that has shown good results in solid tumors,” he said. 

While CAR T-cell therapies have been game-changing in blood cancers, they have largely fallen flat in solid tumors, which comprise about 90% of cancers, he said. TIL therapy is a one-time treatment with the potential to cure solid tumors — some treated patients have been cancer-free for a decade or more, Bock said.

 

Amtagvi will cost approximately $515,00 per patent before insurance and discounts. The FDA signed off on the therapy based on its phase 2 results, but Iovance is following up with a phase 3 confirmatory trial, which will include patients with melanoma that can’t be surgically removed, has spread to other parts of the body or was previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. 

While Amtagvi will give hope to patients with no other treatment options, it may also make even better treatments possible. 

“It will blaze this trail for others to follow on with enhanced next-generation products. I think those will be where we really see some dramatic impacts of TIL in the overall treatment of solid tumors,” Bock said.

Harnessing the immune system

Patients receive Amtagvi in authorized treatment centers where TILs are extracted and expanded using a proprietary process that takes around 22 days. The patient then undergoes lymphodepletion to kill existing T cells before doctors infuse them with billions of beefed-up cells, accompanied by a short course of high-dose Proleukin, an interleukin-2 (IL-2) product Iovance acquired in 2023 from Clinigen Limited. The IL-2 helps the infused cells transition from the controlled lab environment into the body, Bock said. 

Treatment can result in low blood counts, infection and other organ-related complications that can be serious — risks the FDA highlighted in a black box warning. The accompanying IL-2 regimen can bring its own risks, too. 

“The issue with high-dose IL-2 is that it carries its own toxicities and is a difficult treatment for patients to handle,” Bock said. 

Companies developing next-generation TIL treatments are working on alternatives to IL-2, which could reduce potential side effects. The lymphodepletion process may also be problematic. In December, the FDA placed a clinical hold on an Iovance lung cancer trial after a patient died, potentially related to this process.  

A difficult development road 

One reason it took so long to bring a TIL treatment to market is due to one of its cancer-fighting strengths, Bock said. Unlike CAR-T cells, which have to be engineered, the body naturally deploys TILs to infiltrate a tumor’s layers to fight the cancer. The challenge is that TIL cells can get “beaten down” in the process, Bock said, and the tumor evolves to avoid or repress them. 

“They don’t have the fortitude to contain the cancer. So, the goal [with TIL therapies] is to enhance and multiply them to turn them into an army capable of a successful attack,” Bock said.

TILs are also polyclonal and can recognize many targets on cancer cells. But while that makes them alluring as a therapeutic, it also created regulatory hurdles and the FDA had to hammer out a way to regulate this new kind of drug without a predefined target, Bock said.

TILs in the pipeline 

Several other TIL treatments are currently in the pipeline, and many also target melanoma, Bock said. But in theory, TILs have the potential to work against a broad range of solid tumor types. For the next generation to be effective in other cancers, better manufacturing methods will be needed to fortify TILs for battle, Bock said. 

While much of the work on TILs still happens in academic research centers, several companies, such as Turnstone Biologics, Lyell and Instil Bio are testing second-generation TILs, and assessing the modality against targets including breast, colorectal and ovarian cancer. Iovance is also targeting cervical cancer, non-small cell lung cancer, and head and neck squamous cell carcinoma.

Now that the FDA has approved Amtagvi, Bock predicts investment in TILs will surge, much like it did when the FDA approved the first CAR-T cell treatment. 

“It's hard to be the first, but what's exciting is that after you're done with the first there's a trail there for others to build upon and improve upon,” Bock said.  

For patients in need of revolutionary CAR-T cell therapies, time is not a luxury. And even though they offer a shot at a cure, the time it takes to manufacture a treatment can be a matter of life and death. 

To speed delivery of its personalized immunotherapy Yescarta, Kite Pharma recently got the FDA to sign off on a new manufacturing process that will shave two days from its median turnaround time. 

“It’s really exciting because these patients have an aggressive disease, and every day matters,” said Cindy Perettie, executive vice president at Kite, which is a part of Gilead Sciences.

The manufacturing process for CAR-T therapies is complex. It starts by extracting the patient’s white blood cells, which are then modified to produce surface proteins called chimeric antigen receptors that help immune cells target the patient’s cancer. It takes upwards of 18 people to carry out the various manufacturing steps, Perettie said.

Kite officials expect it will now take around 14 days from a patient’s cell collection to infusion — a reduced timeline that not only helps patients, but gives the company an edge over competitors. It may also position the lymphoma therapy to withstand competition from a crop of “off the shelf” allogeneic treatments working their way through the pipeline, said Perettie. Allogeneic treatments use donor cells to create a less expensive option that don’t require cell collection from the ill patient, but can trigger an immune reaction, which has hampered development.

Even with an off-the-shelf option, patients can still wait weeks for a scheduled treatment, and Kite aims to further whittle down the turnaround time, Perettie said. 

“There’s this sense of urgency. Every patient matters. Every day matters. And that's allowed us to get to this industry-leading manufacturing turnaround time and we're not going to stop here,” Perettie said. “We have another set of efforts ongoing and I hope by the end of the year, we're able to announce again that we can shorten it even further.”

Innovating next-gen approaches

Gilead acquired Kite in 2017 for $11.9 billion to bolster its market position in cell therapy. Perettie said the deal gave Kite the best of both worlds, allowing it to remain separate but giving it access to Gilead’s extensive resources. The company kept its singular focus on CAR-T, sparing it from having to make portfolio tradeoffs that detract from its mission. 

“We have the opportunity to solely focus on CAR-T, and I think that has allowed us to serve more patients,” she said. In addition to Yescarta, Kite has a second approved CAR-T therapy, Tecartus, for patients with relapsed or refractory mantle cell lymphoma and acute lymphoblastic leukemia.

To date, Kite has treated more than 19,500 patients with its CAR-T therapies. The goal now is not only speed but broadened access. Currently, only 2 in 10 American patients who could benefit from CAR-T get the treatment, Perettie said. 

“This is a potentially curative therapy for almost half of the patients. It’s insanity to me that we’re unable to reach more patients,” she said. 

Because CAR-T treatments are only administered in authorized facilities — there are 135 in the U.S. and 400 worldwide — oncologists sometimes don’t offer it. Most authorized centers are academic medical centers, but the majority of people with cancer — 70% to 80% are treated in community practices, Perettie said. 

Kite is building partnerships with hospitals that are affiliated with community oncology practices to give more patients access and to encourage treatment referrals.

New disease targets

Kite officials also want to improve their existing CAR-T treatments and broaden their applications. 

“The last five years have been absolutely amazing,” Perettie said, adding that the company aims to maintain its market leadership and serve more patients. 

“Part of that has been focused on expanding both our Yescarta and Tecartus labels so that we can move into earlier lines,” she said. 

Data shows survival rates rise when the treatment is started sooner, possibly because harvested cells and the patients are healthier, so gaining approval to start treatment earlier is a goal. 

Kite is also working to improve its existing therapeutics and is exploring three modified versions of Yescarta aimed at improving safety and efficacy, Perettie said. 

“We have three constructs that are in phase one right now and we're going to pick the winner at the end of the year, and rapidly advance it,” she said. “The early data looks quite promising.”

CAR-T therapy safety recently got additional scrutiny when the FDA moved to require a black box warning on CAR-T treatments to alert patients that they may trigger secondary T cell cancers. Perettie said this is something the company will monitor, but so far, hasn’t seen evidence its drugs triggered T cell malignancies, and the risk of these cancers appears to be lower in CAR-T than from traditional chemotherapy. 

Initially there were some concerns the FDA warning would scare patients from taking these treatments. 

“But we haven't seen that,” Perettie said. 

She does see room to expand CAR-T to other areas. 

“We’re also doing a lot of work in solid tumors and beginning to look at autoimmune approaches,” Perettie said, pointing to compelling data related to autoimmune diseases. 

“We’re seeing patients with highly refractory diseases like lupus, myositis and multiple sclerosis having profound responses from CAR-T,” she said. 

The company also recently inked a $285 million deal with Arcellx to exercise its rights to the ACLX001 ARC-SparX program and expand into multiple myeloma, which affects about 180,000 patients in the U.S. 

“We expect to have pivotal data at the end of this year,” she said. 

About 20% of multiple myeloma patients are Black, so the company is working to ensure that clinical trials enroll the right mix of people and to establish treatment centers in communities with the greatest need, Perettie said.

“Our purpose really is about using that singular focus to advance care for patients and making sure that we have a transformative option,” Perettie said.

Newly appointed CEOs often step into existing companies with long-established cultures, making change difficult.

At Mural Oncology, however, CEO Caroline Loew is seizing the opportunity to build the company’s culture from the ground up.Alkermes officially spun out Mural in November as an independent, publicly traded, clinical-stage immuno-oncology company with $275 million in committed funding. The move allowed Alkermes to become a “pure play” neuroscience company while Mural focuses on cytokine-based immunotherapy, especially for cancers with limited treatment options.

Its lead candidate, nemvaleukin, is currently in registrational trials in advanced melanoma and platinum-resistant ovarian cancer. Nemvaleukin is an engineered variant of the immunotherapy interleukin-2 (IL-2), allowing it to treat cancer without the toxicity that’s typical of IL-2 therapies. The FDA granted nemvaleukin orphan drug and fast track designations to treat mucosal melanoma, as well as fast track designation for platinum-resistant ovarian cancer in combination with pembrolizumab.

In addition, nemvaleukin is in clinical-stage research for advanced solid tumors. The company also has two programs in discovery.

Leading a spinout company means Loew gets the best of both worlds: Established drug candidates and a chance to build the culture from the ground up.

“We’re taking a company that's kind of mid-flight and establishing it as a fully fledged, independent biotech,” she said. “It’s [an] interesting, hybrid-type situation.”

Loew has leadership credentials for the task. In fact, she said her “superpower” is the ability to think and act strategically. A scientist-CEO with a background in organic chemistry, Loew most recently served at the helm of Glympse Bio, which merged with Sunbird Bio in August. Prior to that, Loew was vice president, head of R&D strategy and planning at Bristol-Myers Squibb, and has also held leadership roles at Merck & Co. and PhRMA.

At BMS, Loew was particularly involved in the company’s reprioritization on cancer therapies. And although Loew called her time in oncology drug development and witnessing the rise of immuno-oncology therapies “thrilling,” she also viewed the plateau of response rates as an opportunity for next-generation cancer drugs. 

Coming to Mural was about this “unfinished business” and her desire to advance new mechanisms.

“I have very deep experience both building R&D strategies, as well as executing large portfolios,” she said. “As I come into the company, I'm focusing a lot of my efforts strategically … thinking about where we're going, what's next and how we build for the future.”

She believes the CEO role has three pillars — internal operations, external engagement and developing culture — and is intentional about executing on each piece while maintaining a focus on the patient.

“This is a company that can deliver that next wave of IO agents. It's not just about nemvaleukin. It's about this whole possibility of opening up that future for patients,” she said. “We're building this big future company, and we have incredible conviction.”

PharmaVoice talked with Loew about her leadership philosophy and strategy for building culture at the newly formed company. 

This interview has been edited for brevity and style.

PHARMAVOICE: How do you approach being CEO?

CAROLINE LOEW: I think about, very consciously, how much time a week I spend doing [certain tasks]. That maybe sounds a bit prescriptive, but it helps me make sure I spend the appropriate amount of time as a CEO taking care of what I feel are the important pillars of my role.

I'm a classic person who's very results oriented, and I prioritize critical activities. I think whether you're a small company or a slightly larger company like us, when you're working in cutting-edge science, there's always this enormous temptation to focus on something new that comes up and to get distracted. And one thing I think is very important … is to say, ‘That's super interesting, but that's not what we have to do today.’

Stay focused on executing priorities. That sounds simple, but you would be surprised how often organizations trips up because of distractions.

You said your superpower as a leader is the ability to think and act strategically. When have you done that in your prior roles?

Some of the things I am most proud of in my career is being given the opportunity to — with a blank sheet of paper — look at strategic opportunities for the organizations I have worked for [and] identify things that have not necessarily been previously seen that have dramatically changed the direction of a company.

When I joined BMS … I got to look at the portfolio strategy. At the time, BMS wasn't deeply engaged in oncology. The first thing I did … was assess the entire BMS portfolio and put forward a proposal for how we should prioritize our portfolio. This ended up with BMS increasing their investment in oncology around 30%, and that led to them being the leader they are today.

It was like turning a supertanker. It wasn't just a decision to upend investment. We had to, of course, reprioritize. We weren’t equipped as an organization to operate in oncology, so we rebuilt our operating model. That's an example of big-picture thinking: How can you radically change what you do as an organization and your position as organization?

Why do you believe in Mural’s science and approach?

Immuno-oncology has really revolutionized the treatment of oncology, but response rates have plateaued around 30%. I think about this as the unfinished business of oncology drug development, and when I saw Mural’s data and the approach we’re taking to protein engineering, I realized that we could be uniquely suited solving this issue. What we’re doing at its heart is simple — we’re taking the ‘known known’ of native cytokines, and using our protein engineering to leverage their potency while overcoming issues like tolerability. Nemavaleukin, our recombinant IL-2, is an example of this, where we’ve generated compelling data in both mono and combination therapy, and have recapitulated the responses of high dose IL-2. We’ve also used the same approach for our preclinical programs — an IL-18 and an IL-12 — where we expect to nominate candidates this year.

You’re intentional about establishing culture. How are you doing that at Mural?

First of all, it's a science-first, patient-first organization. Those words are kind of trite. People say that a lot. But it means, at its heart, that you will make decisions solely guided by science and the patient. There are sometimes extremely hard decisions you have to make in development to progress assets or not progress assets. When you are always guided by what the science says and what's best for the patient, it’s such a clarifying perspective.

The second piece is it's a collaborative environment. Drug development is a team sport. It requires many people to come to the table and to work together without prejudice. They need to be sitting around the table making decisions about some very complex science. We need those teams to be very high functioning.

The third piece is that it’s an inclusive organization. By inclusion, we're not just talking about diversity and inclusion. It’s important to listen to every voice. Sometimes the best ideas are the contrarian ideas. It's where the [research assistant] feels able to say, ‘I saw something in this data I think we should pay attention to.’ They’re the people who are maybe closest to the research. Every voice is important. Every voice is heard. And you bring those voices into discussion.

You have to do all of those things. You don't exclude people in meetings. You make sure information is transparent and shared. You make sure when people speak up, you listen to them and you do something about it.

I walk that walk. My door is open. I let people come in and talk to me. It’s not about writing it down on a piece of paper. It's about doing it every single day and expecting everyone to do it and holding people accountable for doing it. There's no two ways around it. You live it. You help people live it.