After years in the industry, Isaacsohn identified gaps in drug development and established a company to solve them.
CinRx co-founder and CEO Jonathan Isaacsohn, MD, FACC, wants to speed up the drug development process and provide medicines to patients faster than historically possible. To achieve this, however, his company will never bring an actual product to market. That's not his MO.
After working in the industry for several years, Isaacsohn decided he had seen enough failures in the drug development process. With more than 90% of drugs from biotech companies failing, he took his 30-plus years of experience in the industry and created a solution that would improve the process. The objective was to use abandoned or repurposed drugs that had not been optimized by other companies and create an entire functional company around each product to fully research and develop it to its full potential.
"Many drugs are discontinued because of problems that could not have been anticipated," Isaacsohn says. "Safety issues, lack of efficacy, lack of benefit over and above other approved drugs, are all reasons to be unsuccessful, but so many drugs fail because of ill-conceived strategies and poor execution. That is the driving force behind why we conceived CinRx, and what we aim to solve in the model that we put together."
This model includes several biotechnology companies all supported under one dedicated funding system which Isaacsohn says helps accelerate the process. CinRx is not just a financial investor in these companies. Instead, it establishes a fully functioning company around each candidate and helps drive its success. Most VC-funded companies receive outside funding and operate on their own.
"At CinRx, we do a fair amount of capital raising at the holding company level, but there's an integration between that money and the execution," Isaacsohn says. "That is quite differentiated from the general model of how biotechs get funded."
"We bring funding into the holding company, and we use that funding to help us establish companies or partnerships," he says. "Ultimately each company follows a trajectory appropriate for that company to a point of exit, wherever that may be, early in the process or later in the process. We never intend to be a pharma company."
As an example, the recent sale of CinCor to AstraZeneca was one of CinRx's first steps toward realizing the company vision, which was set in motion nearly eight years ago when CinRx was founded in 2015.
In 2019, CinCor entered in an agreement with Roche to acquire the rights to a novel aldosterone synthase inhibitor (ASI) compound, CIN-107 also known as baxdrostat.
CinCor conducted phase one studies, safety studies, and a proof-of-concept study. The positive results showcased the value of the drug, and that caught AstraZeneca's attention, who bought the portfolio company for $1.9 billion this February.
"What happened with CinCor actually validates the model that we work in," Isaacsohn says. "Each one of our companies ultimately will find a new home."
Other companies under the CinRx umbrella include CinDome, CinSano, Cinphloro, and CinFina.
As Isaacsohn mentioned, CinRx also operates a second model by partnering with existing companies that, for whatever reason, don't have adequate capacity to develop the drug on their own. CinRx partners with the company by investing in it, so it has "skin in the game," and it then drives the development on the other company's behalf. Two of these partnerships currently exist: vTv Therapeutics and Retromer Therapeutics, bringing the total number of portfolio companies CinRx is working with to seven.
It is this multiple shots on goal approach in the drug portfolio that expedites the process. "By sharing resources across companies combined with an efficient process, we're being good shepherds of the funding," Isaacsohn says.
CinRx's pipeline of transformational medicines include therapies for diabetes, gastroparesis, IBS, metabolic and neurodegenerative diseases, and oncology.
Being the CEO of CinRx puts all of Isaacsohn's previous work experience to good use. Throughout his career, he has worked in drug development from early phases through global submissions in various therapeutic areas. He is also a cardiologist, trained in internal medicine and cardiology at Harvard Medical School, and has taught on the cardiology faculty at Yale Medical School. Isaacsohn was one of the founders at the ground floor of global CRO Medpace and worked there for 14 years, until it was sold.
CinRx works closely with Medpace as its development arm, testing and developing the compounds it acquires. This keeps CinRx on the cutting edge of drug development, Isaacsohn says, as Medpace has many of the resources needed to develop a drug and as drug development has evolved, so have they.
After the sale of Medpace, Isaacsohn served as CMO for Teva Pharmaceuticals where he drove development of Teva's specialty drugs and the new therapeutic entities initiative across all therapeutic areas.
This collective experience prepared him well for the challenges at CinRx.
"I have been in this industry for a long time from all different vantage points, and different roles. I'm a trained cardiologist and was in academic medicine. I did the first human study with Mevacor. I was a principal investigator on hundreds of trials. I was among the founding group that established the CRO Medpace. I ran the medical and regulatory side and that's where I got exposed to biotech companies. I did literally hundreds of programs on behalf of other biotech companies, and that's where I learned the trade."
Isaacsohn believes himself to be a democratic leader and he aims to keep the organizational structure flat, giving everybody a role, and a chance to participate in decision making. "We don't have the kind of hierarchy that makes people feel they need to keep quiet, or they can't express themselves. We value everybody's opinion. It's very much a family feel in our group."
Isaacsohn credits his leadership success to his varied experience. "I've been around the block," he says. "A lot of it just has to do with experience."
Editor's note: This story was updated to correct the spelling of Cinphloro. Updated 3/28/23.
The company prioritizes unmet needs for women in contraception, fertility, and vaginal and sexual health.
Sabrina Martucci Johnson never planned on being a founder and CEO of a women’s healthcare company, but after identifying gaps in women's healthcare, she asked herself, “If not me, then who?"
"I'm not one of those people who always wanted to be a CEO," she says. "But I had a light bulb moment: if I don't do this, it's not going to happen."
Over the years, Johnson had always championed for women in her volunteer and charity work, supporting philanthropic activities surrounding STEM education for women, domestic violence awareness, and women's healthcare issues.
On the professional side, Johnson spent her entire career in the drug development industry, in a variety of roles. She began as a research scientist with Baxter Healthcare and went on to hold marketing and sales positions there.
Later, she held C-suite positions, including CEO, CFO and COO at WomanCare Global Trading, a specialty pharmaceutical company in female reproductive healthcare, and before that she served as CFO of Cypress Bioscience, a publicly traded pharmaceutical company.
"I felt there should be a way to match my extracurricular passion with what I do professionally," Johnson says. "There are all these needs of women that are not being met. So, I put my money where my mouth is, and started Daré Bioscience in 2015.
"In addition to aligning her life goals and working toward filling unmet needs for women, Johnson saw the business sense of investing in women's health. Market research shows that only approximately 1% of healthcare research is invested in female-specific conditions beyond oncology, and women’s health conditions outside of oncology comprise less than 2% of the current healthcare pipeline.
Yet, women’s health products outside of oncology make up 27% of the total number of blockbuster products (products that each have over $500 million in annual sales) and contribute 35% of the total sales dollars generated by blockbuster products. "This is why investment in women’s health is efficient and impactful in terms of translating dollars invested in R&D to ultimate revenue generated, and therefore, not only good for 50% of the population, but it is also a good business model," she says.
The company prioritizes unmet needs for women in contraception, fertility, and vaginal and sexual health. Daré’s first FDA-approved product, Xaciato, is a vaginal gel for the treatment of bacterial vaginosis in female patients 12 years and older, which is under a global license agreement with Organon.
Daré’s portfolio also includes potential first-in-category candidates in clinical development: Ovaprene, a novel, hormone-free monthly intravaginal contraceptive whose U.S. commercial rights are under a license agreement with Bayer; Sildenafil cream, a novel cream formulation of sildenafil to treat female sexual arousal disorder utilizing the active ingredient in Viagra; and DARE-HRT1, a combination bio-identical estradiol and progesterone intravaginal ring for hormone therapy following menopause. There are currently no FDA-approved products that continuously deliver this type of hormone therapy with both estradiol and progesterone together.
"It was a little bit shocking that there was no FDA approved product that met the guidelines that the medical experts in the space recommend for hormone therapy, which is the need that the two hormones be administered together," Johnson says. "When we started the company, this is why hormone therapy for menopause was high on our list."
DARE-HRT1 could become the first FDA-approved monthly intravaginal ring delivering such therapy. Due to its positive early phase results, the company has been cleared by the FDA to advance directly to Phase 3.
Johnson said that even though it was out of the ordinary, the company decided to ask the FDA if it would consider allowing them to go straight to Phase 3 trials.
"After the trial results we started discussions with the FDA to propose that we just go right to a single Phase 3 so that we can get this product moving forward and into the market to women," she says.
The trail blazer didn't think it was much of risk to take the request to the FDA, as long as they could pass the 'red face' test, meaning they had justification for asking and the ability to prove it. This was a case of 'you never know until you ask', she says.
"We made an ask that wasn't the normal path, but we scientifically could justify it," she says.
"If you can scientifically make a case for something, there is room to color outside the lines, and DARE-HRT1 is a great example of that."
If the FDA denied the request, Johnson reasoned, Daré would be in the same place as if it didn't ask. But surprisingly, the FDA said yes.
"We were really pleasantly surprised that the FDA came back and said yeah, that's reasonable," Johnson says. "Now we have a lot of work to do to get ready, beginning with formally filing the IND."
Currently, Daré's portfolio only contains products that aim to deliver drugs in a way that's never been delivered before and pushing the envelope on indications that haven't been studied before. Thinking outside the box this way is the company's credo and striving to be first in these areas is not without challenges.
"We are all about the firsts, and firsts are hard," she says, "It's challenging but it's such an incredible opportunity. And I would also say, in the same breath, it's the most fun program to work on in our portfolio because while it's hard to be first, it is also fun to be first and to get to set the stage and blaze the trail."
For example, the company is developing a cream formulation of sildenafil --the same active ingredient in Viagra--for women with female sexual arousal disorder. There's nothing approved for this indication. "We are really blazing a trail getting all the work that goes into a brand-new indication: getting the alignment on what to study, what are the endpoints. Like how to design a clinical trial for this, for starters."
Johnson keeps the company focusing on firsts by creating opportunities for employees to be free and open with brainstorming new ideas and solutions. It is cliché, Johnson says, but to her, there really is no bad idea or dumb question that employees can pose.
"I try really hard to be a very authentic leader," Johnson says. "I have a very authentic style and create very much a culture of dare to be different and be bold. Let's push the envelope. It's okay to suggest something that hasn't been done before. It's okay to put those ideas out there. I very much try to create a culture of 'let's think outside the box and be aggressive.'"
Personal tragedies involving family and friends motivated this CEO to launch Peptilogics.
When thinking of life-threatening surgical risks, hip or knee replacement does not immediately spring to mind. Maybe it should.
No one knows that better than Jonathan Steckbeck, CEO and co-founder of Peptilogics. The replacement procedures aren't necessarily risky, but the infections that can occur after surgery are. Antibiotic resistant bacteria --often staphylococcus aureus-- can accumulate on the hard surfaces of the prosthetic and cause infections that are very difficult, if not close to impossible, to eliminate. This is what can cause knee replacement and other joint replacement surgeries to turn deadly.
Most prosthetic joint infections (PJI) are the result of bacteria already present in the body or introduced during the surgery or other procedures. The usual treatment is additional surgery and antimicrobial therapy, often taking place over a span of many weeks or months. These infections put the patient at a high risk of morbidity and the five-year mortality rate after catching one of these infections is 25%, according to Steckbeck.
"That's not common," he says. "Ever since we've had antibiotics, we've been able to control most types of infections. That this can’t be controlled in this day and age is alarming."
Steckbeck has seen loved ones struggle with PJI, including his father-in-law, who died from antibiotic resistant infection, and a family friend—a fit Navy fighter pilot who required multiple surgeries over 18 months before he was cured of the infection. Steckbeck says the pilot fears that the infection might return.
These tragedies motivated Steckbeck's first entrepreneurial venture. In 2013 he left his work in HIV research and launched Peptilogics.
"There's no effective drug to treat this infection," he says. "When my father-in-law passed, I thought there must be something more we can do to solve this problem."
With a PhD in biochemistry and molecular genetics and an MBA from the University of Pittsburgh, Steckbeck turned his research mind to business. He saw an opportunity to not only improve patient lives, but to also fill an unmet healthcare market need.
While the patient population for PJI is small, controlling devastating infection is life altering for the patient. It can also reduce costs by negating the need for 12 to 18 months of expenstive post-operative treatment. "Per patient direct costs are in the $100,000 range, and the total cost per patient for certain joints can be in the $500,000 range," Steckbeck says. "PJI ends up being a really large economic burden. We have an opportunity to bring a good therapeutic to patients and create a market around that."
More than 1 million total joint replacements are performed in the U.S. each year, a number projected to grow to nearly 4 million by 2030 due to the aging, active population.
PLG0206 is Peptoligics' tool to address persistent bacterial pathogens. It attacks bacterial pathogens within the biofilm that evade standard-of-care antibiotics by targeting and disrupting bacterial membranes to trigger bacterial cell death. If approved by the FDA, the anti-biofilm, anti-infective peptide therapy will be the first specifically indicated for the treatment of periprosthetic joint infection.
Still in investigational stages, PLG0206 has been granted FDA Orphan Drug, Fast Track and Qualified Infectious Disease Product Designations for the treatment of PJI. Peptilogics began dosing patients in October 2022 through its LOGIC-1 clinical trial.
The importance of computational technology
As Peptilogics designs better therapy for PJI patients, it is also pioneering machine learning methods and artificial intelligence that create previously unattainable efficiencies and accuracies. This works not just in biotech, Steckbeck says, adding that any business can benefit from using computational technology, even hospitals. The challenge is finding the right application to solve the problem.
"Using computational technology is going to be increasingly important no matter what business you're in," he says. "Companies need to have a base-level understanding of how some of these technologies work, so that they can apply them more effectively. It's how do you build and understand which tools can be applied to your problem, so that you can answer the question most effectively."
At Peptilogics, its computational design accelerates the discovery and development of peptide therapeutics by combining peptide research, AI, and machine learning to quickly extract insights from biomedical data. Traditionally, the industry uses more of a screening method for discovery, which takes much longer.
"Through advances in peptide synthesis technology and computational design, we can move beyond broad, random screening to chart the universe of functional peptides and design novel therapeutics," Steckbeck says. "We are trying from the very beginning to design for the characteristic that we want, better, faster, and cheaper."
These are the technologies that make scalable peptide drug design a reality, Steckbeck says.
"Using modern techniques around machine learning is how we believe we're going to be able to bring more solutions to patients."
Lessons learned in first biotech venture
Steckbeck credits his MBA for honing his entrepreneurial skills and giving him the balance needed to start a biotech from scratch. When speaking with others about to enter the field, he encourages them to broaden their education to include business.
"I tell grad students that learning business on a broad level is important if you think you might go the entrepreneurial route. It's a hard transition from the super detailed work of science to pulling back 30,000 feet and telling the business story, and a background in business helps," he says.
The biggest lesson he has learned, Steckbeck says, is how important it is to build a strong team. He suggests finding the best people possible for each role. "The biggest lesson I've learned is how important having a good team is," he says. "My job became much easier with a good team supporting me."
An additional benefit is if that team consists of "people who are actually really fun to work with, because a lot of what we do is really, really hard. It is hard on top of hard. If you don't have a good group of people that you want to work with every day, it's going to be that much harder," he says.
The physician-scientist and serial biotech entrepreneur uses team sports experience to lead his innovative biotech.
On the soccer field, you will find David Kirn, MD, co-founder, co-chairman and CEO of 4D Molecular Therapeutics (4DMT), playing central midfield, the position that pulls everyone together to set up goals.
Centerfielders are offensive team leaders who must constantly pass the ball to teammates from all over the field. According to the sports coaching site, planet.training, scientific data shows that central midfielders are adept at passing the ball, with the ability to use either foot equally well, and provide efficiency, creativity, strategy and strength to the game.
"My charge on the soccer field is to pull all the different parts together and make everybody else look good. That's what the center midfielder does," Kirn says. "I'm not a forward, scoring all the goals and getting all the attention. I'm doing the hard work."
As CEO of 4DMT, a biotechnology company working on adeno-associated virus gene therapy vectors, Kirn functions the same way—setting others up for success by creating a culture of teamwork, the flexibility to learn from mistakes, and big wins.
Kirn started his off-field career as a physician nearly 20 years ago, and considered a profession in academics, but his innate entrepreneurial drive led him to launch six startups over the past couple of decades, including Jennerex and 4DMT.
That drive and his love of team sports honed his leadership skills to include remaining calm during moments of crisis, he says.
"I've always loved team sports and once I started working in biotech, I realized the process is just like a team sport. Everybody's pulling in the same direction," he says. "Everybody's focused on the same goal, it's all about preparation and execution."
For example, Kirn relates an experience at 4DMT that happened around four years ago, when a well-running development process for a new candidate hit a snag. Instead of panicking, Kirn kept a cool head, and redirected his team under pressure. The company had just closed on a $90 million Series B financing round and had entered into partnerships with Roche and Pfizer. The company was preparing for its AAV gene therapy asset for choroideremia, a rare chorioretinal dystrophy causing progressive vision loss mostly in males, to enter into its phase 1 clinical trial. At that point, the company had been working at least four years already with physicians, patients, and investors to prepare the candidate for development. "Everyone was excited about the prospect of this therapy," Kirn says. "Patients were waiting."
Then, there was a glitch. "I got a phone call at four o'clock on a Friday from my head of manufacturing," Kirn says. "An assay that had always tested normal had come back abnormal."
Kirn's first reaction was to assume the test was faulty, as the results had never come back wrong before for the assay.
"I said to everyone, 'stay calm. There's no way that's true,' " he says.
However, after further testing, he and his team discovered the abnormal result was very real.
Kirn had to inform the investors, partners, physicians, patients, and the patient advocacy organization the company had been working with, that not only was the gene therapy not going to clinic in four months, but the trial could be delayed up to six to 12 months longer.
Jump heading the problem, Kirn immediately gathered his team together to scrutinize what had gone wrong, with the assurance that no one would be blamed for having made a mistake.
"To get to the bottom of that problem, we had to convince people that no one would be pointing fingers, nobody would be blamed for what had gone wrong," Kirn says. "We called emergency meetings; we hunkered down. We went through line by line by line of a 100-step process. And then we got to this one step, and we discovered a design flaw in one out of 100 reagents involved."
This was the point when the team really could have gotten frustrated and discouraged and started playing the blame game.
"It could have been a horrible outcome, but in the end, it made us much stronger as a company," Kirn says. "It made our development engine much stronger. We've never had a delay like that again, and we're now running the most efficient engine in the business. That means every single time we do anything in this company, we look at every single step very rigorously. One of our guiding principles is 'relentless preparation and execution'. And that's all the result of how we resolved this one crisis moment."
It took 10 months instead of four, but the product candidate 4D-110 entered the clinic and today that program --an ongoing Phase 1 dose-escalation clinical trial -- is running effectively and benefiting patients.
Having played team sports all his life, Kirn says soccer in particular taught him about the important balance between offense and defense, about never giving up, and executing well under pressure.
Kirn's leadership style translates across industries
At 4DMT, the transformative precision genetic medicines being developed create excitement and momentum among employees, Kirn says. Having a clear strategy on how the company is going fulfill its vision is also key to its culture.
Kirn says building this type of excitement has to start at the top, and if it does, any organization can benefit from it.
"You have to create a culture that embraces innovation, doing things smarter and better," he says.
"I would say that is directly applicable to other businesses."
Raising the engagement and interest of stakeholders is possible by using approaches that are superior to the competition.
"If I ran a hospital, for example, I would put together a compelling vision of how the hospital is going to change the world of care by doing big things, along with setting clear objectives and a clear strategy to get there," Kirn continues. "That's a vision that gets employees excited. It gets physicians excited; it gets patients excited, and then they all want to go on that journey with you."
This way, more patients will want to come to my hospital because I've got innovative products, and people are going to want to work for me and stay with me in a competitive work environment for the same reason. And frankly, donations to the hospital are going to go up significantly because you're doing something exciting. And you say hey, we need money to build a new facility to do this exciting new research. it's really applicable to any organization including a hospital," he says.
Success requires employees to go above and beyond to bring a goal to fruition.
4MDT has four guiding principles it plays by: one of them is breaking boundaries, and questioning the status quo; looking beyond yourself and keep a larger picture of
patients, their families, the 4MDT team, their families; and as already mentioned,
prepare and execute relentlessly.
"The fourth is 'dare to cure' " says Kirn. "That means doing more than striving for just incremental benefits but stretching for breakthroughs and taking calculated risks to achieve them. We create novel treatments that are going to radically change patients' outcomes."
It is with these principles that Kirn has helped his team score many important goals-- in the field of genetic therapy, as well as on the soccer field.
A focus on training and optimizing middle management are the keys to her success.
To say Terry Weber has had a diverse career path is an absolute understatement.
With successful leadership roles across several industries, from oil and gas to psychiatry, from auto parts to lingerie, and currently as CEO of healthcare company Biote Medical, Weber brings her leadership skillsets everywhere she goes, and she has developed some tried-and-true strategies that work across any operation, including hospitals and healthcare facilities. The one consistent thread through all three decades of experience is growth.
Throughout her career, Weber has been responsible for building from $100 million to $2.5 billion companies in annual sales. Companies appearing on Weber's resume include Amen Clinics, brainMD, Frederick's of Hollywood, Mattioli Weber Consulting, Advanced Auto Parts, and several more.
What she learned by scaling multiple businesses (she grew the auto parts retailer from three stores to 2,000; increased Frederick's of Hollywood's e-commerce business from $500,000 to $7.8 million in less than 18 months), was that standardizing education across all staff levels helps raise everyone's competence and ensures the success of the business.
"Whether someone is trying to improve the interaction between physicians and patients, or building the skills of middle management, or scaling deliverables, training is key," she says.
Training acts as the rising tide that lifts all boats
Biote provides preventive healthcare through the delivery of personalized hormone therapy delivered by Biote-trained medical providers. The treatment works by placing pellets under the skin which supplies a steady dose of hormones to the body. Biote runs a program that trains practitioners how to identify and treat early indicators of hormone-related aging conditions.
"We function similarly to a hospital in that we have 5,300 providers who are contracted with us," Weber says. "We are both striving to influence the behavior of an independent practitioner, in order to create a satisfactory level of excellence."
This challenge of educating stakeholders is an issue across all industries and is particularly important in healthcare.
"Much of my career has been about getting better provider/patient interaction, which is a big issue for hospitals," Weber says. "For five years, I worked trying to get psychiatrists to relate to their patients."
The problem Weber faces at Biote is that physicians are not taught about the symptoms of menopause in medical school, so Biote must do the training. "At Biote, we train practitioners to have a conversation that they're not comfortable with having, not even with their wife," she says.
"Only 20% of OB-GYN programs have an elective course in menopause. Other medical programs don't even cover it. That means half of the world is going to their practitioner with menopause symptoms and the practitioner doesn't even know what menopause is."
In fact, in some cultures, menopause isn't even recognized, even though changing levels of estrogen and progesterone in aging women can create more than 34 symptoms, the most common being hot flashes and vaginal dryness.
To solve this problem, Biote created the physician certification program. Weber credits the education piece as being crucial in the continued growth of Biote.
"I took my consumer background and applied it to healthcare," she says. "Number one, you standardize education across the whole platform. Whether it's an OB-GYN or a family practice, or a cardiologist, you teach all of them to the same higher standard of competence. You standardize it like in a franchise, and then you standardize your expectations. For example, we actually put the education requirement in our contracts. It is also in the contracts that we require them to come back for continued training."
Biote also requires that the entire practice staff, not just the physicians, receive training so everyone is on the same page and there can be a smooth transition in transferring the knowledge to the patients. "We mandate that we train the whole office at the same time, and the outcomes are much better for the patient," she says.
Biote recently reached a significant milestone in terms of training; it now has contracts with trained practitioners in all 50 states. When Weber came onboard, the program was operating in only 10 states. "The big story for the company is that it is continually growing, and we haven't had any problem with the recession."
Mid-level management is crucial for change
It is Weber's mission as CEO to steer the company to continued growth. The third quarter report shows revenue of $42 million, an 18% increase year over year. Weber says this growth is driven primarily by the mid-level management in the company. "I know from my consumer background and experience in scaling big companies that my mid-level management is the key to change and growth," she says. "You can't scale or grow quickly, especially in healthcare, without a whole team of mid-level managers who've been trained and allowed to flex their muscles behind you. You're not going to get anywhere without the lower and middle ranks. That's where your change happens."
Weber says at Biote the mid-level group is given opportunities for career growth, to voice their ideas and opinions, hold meetings for their level with senior executives as observers only, and they are given decision-making power, which all helps them "practice" how they would handle situations before they get promoted, or thrown into a higher-level position.
"The real growth is going to happen at that mid-level, that's your talent pool," she says. "You can't just focus on your top-level executives."
Making a similar case for training in a hospital setting, Weber says the focus on rank and file is as important in successful operations of hospitals as companies. "Most entrepreneurs, especially in healthcare, they lean on their cadre of execs around them, but it's that mid-level management, the rank and file, who's going to be your future and you've got to train them now," she says. "The real change has to be operational and it's the nurses who make the day-to-day decisions who need to be involved. That's where transformation happens."
Weber says her aptitude for business started at the age of 12 with a birthday party service, and that did not align with her Irish Catholic family's focus on education. "Most of my family members are teachers with PhDs," she says. "But you know, since I was young, I've always been entrepreneurial."
By the year 2025, there will be 1.1 billion postmenopausal women worldwide, and many of them may end up being grateful that Weber and her entrepreneurial spirit is at the helm of Biote, continuing to create growth and change.
Editor's note: This article was updated on December 5, 2022.
Finding a better way to improve the lives of patients is Tak's lifelong mission.
Editor's note:This article appears in the March 2023 edition of HealthLeaders magazine.
The CEO of viral immunotherapy company Candel Therapeutics, Paul Peter Tak, MD, PhD, enjoys exploring the world with his family, experiencing different cultures, and discovering new perspectives and approaches to both life and business. Adventure travel is his passion, and he has taken his children since they were young on trips, for example, to Borneo, Malaysia, Namibia, and Ecuador. "We've been to many places, from Latin America to Africa," he says.
Tak's family lives internationally; he and his wife live part-time in different countries, as do his four children.
"Half of our children are in the Netherlands, half are in England, my wife is in England, and I commute between England and the U.S.," he says.
This exposure to multiple cultures not only enhances his life, but also provides him with a world view toward business and leadership.
"You always learn from other people, other cultures," he says. "And you can always find better ways of doing something in one part of the world compared to another."
Throughout his diverse career, from physician to academic, from big pharma to small biotech leader, his mission has been steadfastly the same: improve the lives of patients.
In just two years at the helm at Candel, Tak has made great strides toward this goal.
Paul Peter Tak, MD, PhD, is the CEO at Candel Therapeutics. Photo courtesy of Candel Therapeutics.
He has led the clinical stage biopharmaceutical company that develops oncolytic viral immunotherapies to fight cancer. Candel's engineered viruses induce a systemic anti-tumor response against the injected tumor and uninjected distant metastases. In other words, the company is discovering a new way to beat hard-to-treat cancers.
Within that limited timeframe, Tak has guided the ongoing development of two oncolytic viral immunotherapy platforms based on novel, genetically modified adenovirus and herpes simplex virus constructs. CAN-2409 is the lead product candidate from the adenovirus platform and CAN-3110 is the lead product candidate from the herpes simplex virus platform.
Just last month, CAN-2409 earned a nod from European Medicines Agency (EMA) Committee for Orphan Medical Products for the treatment of glioma. In the U.S., CAN-2409 earned FDA fast track designation in June 2021.
At this year's ASCO meeting, Candel's Co-Principal Investigator Charu Aggarwal, MD, MPH, associate professor at Perelman School of Medicine, University of Pennsylvania, presented clinical outcomes from its phase 2 clinical trial for CAN-2409 and valacyclovir in combination with anti-PD-1 or PD-L1 agents in patients with stage III/IV non-small cell lung cancer. Tak is "super excited" about the results, which show that CAN-2409 injected into tumors achieved disease control in 87.5% of the patients in the trial and improve uninjected metastases.
"That means we were able to convert progressive disease into stable disease, the tumors stopped growing, and that is expected to be associated with improved survival," he says. "It's still a relatively small number of patients, but we will have more new data and a new cohort of patients in December this year."
CAN-2409 is also being evaluated in multiple phase 2 and phase 3 clinical trials for brain, pancreatic, and prostate cancers.
In June 2021, Candel reported preliminary clinical data which showed the ability of CAN-3110 to induce immune activation both locally in the tumor microenvironment and systemically in peripheral blood. Data on a new cohort of 11 patients will be presented in November this year.
The promise of these two candidates inspired Tak to take the president and CEO position at Candel, as he predicts they will be transformational in the treatment of hard-to-treat cancers. "I had confidence that both of these two investigational medicines have huge potential and I wanted to lead this company through the massive change to get everything ready for this stage," he says. "It is so satisfying when you can actually advance a new paradigm in science and have an impact on patients' lives, especially as a physician who tries to better the life of patients."
Under his leadership, the company went public in July of 2021 and evolved from an unknown company to a recognized contender in viral immunotherapy with a new discovery platform, the enLIGHTENTM Discovery Platform. It was recently announced that world-leading scientists at the University of Pennsylvania have partnered with Candel in discovery.
Once onboard, Tak set about building a heavy-hitting leadership team, recruiting colleagues from all over the world.
"We have a top executive team and a research advisory board with people like Jim Allison, the Nobel Prize Laureate. Special advisors include the former CMO of Pfizer, Mace Rothenberg, MD; and Carrie S. Cox, one of the top 50 most powerful business leaders in the world," Tak says. Also this year, Candel added Seshu Tyagarajan, PhD, as chief technical and development officer; Francesca Barone, MD, PhD, as chief scientific officer; Jason A. Amello as CFO; and Garrett Nichols, MD, MS, as CMO. Very recently Renee Gaeta; Gary Nabel, MD, PhD; and Joe Papa joined the Board of Directors.
"There's a reason that all these people want to join us, because they see the same potential as I saw two years ago," Tak says.
A born leader
Tak has been an active leader from a young age, organizing groups, teams, and activities even as a child. Lessons about leadership started when listening to his father around the dinner table, and he developed his skills wisely over time.
"I'm open to listening to new ideas, and then I will test them in a rigorous way, and then reject probably 97% of them. But this mindset has helped me to discover and develop new concepts in academia, in big pharma, and also in biotech."
Tak is a firm believer of being accessible as a leader and says the role of the CEO should be largely externally facing. "Part of the job of a CEO in biotech is to talk more about what we are trying to achieve in medicine and in science, so that people understand it," he says.
"As a leader, you need to be able to share, with the external community, the excitement that we feel, including with pharmaceutical companies that could become partners in the future."
Tak's personal motivation comes from his start as a physician, when he wanted to treat patients so that their lives could be enjoyed.
As a treating physician and academic, I have always had a laser focus on improving patients' lives," he says. "At some point, I decided to move to the pharmaceutical industry to have a bigger impact. Imagine what you can achieve if you develop a medicine that improves the lives of millions of patients? In my roles as senior vice president, chief immunology officer, and global development leader of GlaxoSmithKline, I learned a lot about drug discovery and development and how to lead at scale. I have subsequently used my experience as a clinician, academic, and pharma R&D leader to discover and develop new investigational medicines at a faster pace in the biotech environment."
When Tak is not breaking ground on lifesaving cancer treatments, or taking exciting adventure excursions, he says he enjoys partaking in the creative arts. One daughter, perhaps following his creative footsteps, was a professional ballerina and is now an arts student.
“I like the world of art. I like music. I like dancing. I like good food,” he says. “In another life, I would perhaps have loved to have been an artist. However, one uses a lot of creativity in science and leadership."
Editor's note: This story was updated on November 9, 2022.
W. Garrett Nichols, MD, says he is motivated by "building a team of passionate people who are empowered to do their best work in the service of improving survival of patients with cancer."
As a student, W. Garrett Nichols' first love was biology, and he says his decision to pursue a career in medicine was inherent.
"Becoming a physician was a natural way for me to apply that passion to the betterment of others," says Nichols, who in September took on the new role of chief medical officer at Candel Therapeutics.
Nichols received his medical degree and trained in internal medicine at Duke University before earning a master's degree in epidemiology and completing a fellowship in infectious diseases at the University of Washington, after which he was on faculty at the Fred Hutchinson Cancer Research Center and the Head of Infection Control at the Seattle Cancer Care Alliance.
He has served as head of clinical development at ViiV Healthcare, specializing in the development of therapies for HIV infection, and as CMO at Chimerix, where he led the development of Tembexa, an approved treatment for smallpox. He directed multiple global development programs at GSK, including the late-stage clinical trials and global regulatory submissions that led to the approval of Tivicay and its fixed dose combination product Triumeq for patients with HIV. His most recent CMO role before joining Candel was at Istari Oncology, an oncolytic viral immunotherapy company.
HealthLeaders asked Nichols to outline his strategy and expectations for his new role at Candel.
HealthLeaders: What is the biggest challenge you expect to face as the new CMO?
W. Garrett Nichols: With a robust slate of clinical trials in lung, brain, pancreatic, and prostate cancer, my initial focus is to ensure that we are executing effectively across the portfolio. Given that PrTK03 (Phase 3 study of CAN-2409 in prostate cancer) study is intended for registration, I also am planning ahead for the BLA to come.
HL: You have worked at both large and small pharma. Is this experience helpful in your new role?
Nichols: At GSK and ViiV Healthcare, I was fortunate to lead the cross-functional team that developed dolutegravir (an HIV integrase inhibitor) from phase 2 through phase 3, which culminated in global submissions and approvals for Tivicay and its fixed dose combinations, which are now preferred agents for the treatment of patients living with HIV. These positive clinical, regulatory, and pharmaceutical development experiences are transferrable to our goals here at Candel. Small companies, on the other hand, offer the opportunity to build a team and shape its culture, with a focus on innovation and creative problem-solving given the different resources that are deployable in small biotech.
HL: What keeps you motivated?
Nichols: Building a team of passionate people (both within and outside of Candel) who are empowered to do their best work in the service of improving survival of patients with cancer is the highest reward.
HL: What challenge is the industry currently struggling with and how do you solve it?
Nichols: Investment in early-stage development of promising but unprecedented assets remains a challenge. Public-private partnerships that target difficult-to-treat diseases are one tool in my toolkit. I am also always looking for opportunities to utilize creative designs that can demonstrate early proof of concept to stimulate investment from the private sector.
Amello says working in healthcare gives him the opportunity to affect people's lives in a profound way.
As a young man, Jason Amello wanted to be a musician, because he likes how music can reach and positively affect so many people. Instead, he pursued a career in healthcare, which he says gives him a similar opportunity to impact people's lives but in a much more profound way. "I still play music in my personal time, which gives me the best of both worlds," he says.
The 30-year industry veteran has recently stepped into the new role of chief financial officer at Candel Therapeutics. Amello has served in several finance leadership positions, most recently at Saniona AB, a rare disease biotech company. Prior to Saniona, he held finance roles at Akebia Therapeutics, Alaunos Therapeutics, and served 11 years at Genzyme.
HealthLeaders asked Amello to outline his strategy and expectations for his new role.
HealthLeaders: What is the biggest challenge you face in your first 90 days of your new role?
Jason Amello: We at Candel are fortunate to have a strong pipeline of viral immunotherapy product candidates in early-, mid-, and late-stage development across several solid tumor indications. As a result, each of those programs require different strategies, and therefore, have different resource and capital requirements. My goal is to ensure the company's collective resources are aligned and deployed to each program in the most optimal and efficient manner.
HL: How has your experience in both large and small pharma prepared you for this role?
Amello: I was with Genzyme Corporation from 2000–2011 and despite how large and diversified Genzyme became, due to Henri Termeer's leadership and vision, it never lost its entrepreneurial spirit and culture. Teamwork and innovation were paramount, and people were given a broad range of freedom to contribute and add value. As a result, I was able to experience the building and growth of a fully integrated biotech business, spanning early research, drug development, business development, M&A, commercialization of multiple products, and life-cycle management. That has prepared me well for leadership in small pharma. I will use this experience to support Candel in its mission to develop transformational medicines for patients with cancer.
HL: What is the secret of your success? What keeps you motivated?
Amello: Well, I wouldn't call it a secret. There is no substitute for hard work, tenacity, passion and, it goes without saying, amazing teamwork … all that, coupled with the determination to deliver therapies to patients who critically need them. It is both the successes and failures of the past that provide the learnings and pathway for more effective therapies today and tomorrow, and that is what keeps me motivated. We are never done.
HL: What is a current issue the industry is dealing with and how will you address it?
Amello: The capital markets for the biotech industry have seen a significant pull back over the last year, and it has become increasingly difficult for many companies to access the capital needed to develop those technologies in accordance with their current development plans. My goal is to ensure Candel's collective resources are aligned and deployed in the most optimal and efficient manner so that we can execute our strategy and deliver on our milestones.
Editor's note: This story has been updated on October 21, 2022.
Drugmakers, Black Women's Health Imperative press for diversity in the healthcare system.
According to FDA data, in 2020 more than 32,000 people took part in drug trials and 75% were white, 11% were Hispanic, 8% were Black, and 6% were Asian. The aftermath of COVID-19 shed light on glaring health disparities in the system, as access to vaccines and care impacted ethnic minority groups unequally.
In reaction to this spotlight, several pharma companies have pledged to increase their efforts in narrowing the gap in health equity. Pfizer, Johnson & Johnson, Moderna, and Novartis have all been vocal about their efforts, according to a report by media analytics company Commetric. Bristol Myers Squibb, Genentech, AbbVie and Gilead Sciences are also reported to be funding similar initiatives.
For example, Johnson & Johnson and nonprofit Stand Up to Cancer have joined in a $5 million partnership to increase diversity in early-phase clinical trials. In 2020, J&J also launched Our Race to Health Equity, a five-year, $100 million commitment to address the inequities and systemic racism that contribute to poorer health outcomes in communities of color in the United States.
Another example of pharma contributing to the health equity solution is the partnering of Pfizer and clinical research site organization Headlands Research. The two companies plan to launch new research sites in regions with vastly diverse populations to boost diversity in clinical trials. Last year, Pfizer ran a TV ad campaign aimed at increasing clinical trial participation in the black community, called 'Black Community Health Concerns.'
Additionally, the Pharmaceutical Research and Manufacturers of America (PhRMA) is funding a clinical trial initiative, Equitable Breakthroughs in Medicine Development, to enhance diversity with a $10 million grant which will source an 18-month pilot at 10 community sites located in the southern United States. This includes collaborating with three medical schools: the Yale School of Medicine, Morehouse School of Medicine, the Research Centers in Minority Institutions Coordinating Center at Morehouse School of Medicine and Vanderbilt University Medical Center.
The nonprofit Black Women's Health Imperative (BWHI), which strives to improve the health and wellness of Black women and girls, has several pharmaceutical companies as partners. Its core mission is advancing health equity and social justice for Black women, across their lifespan, through policy, advocacy, education, research, and leadership development. BWHI lists Gilead, bluebird bio, Novo Nordisk, Pfizer, Merck, Amgen and many more as partners working towards improving health equity in patients of color.
Linda Blount, MPH, President, CEO of BWHI spoke with Health Leaders about the possible solutions and initiatives that address the health disparities facing women of color.
Black women are vastly underrepresented in clinical research and trials, BWHI reports. An analysis of data from the FDA indicates that in trials for 24 of the 31 cancer drugs approved since 2015, fewer than 5% of study patients were Black. Without more diverse participation, research cannot be confident that new precision treatments will be effective for all patients.
To narrow the seemingly immovable gap (ratio of blacks to whites in clinical trials have stayed steady since 1985), there are several changes in the system that need to be made, according to Blount.
"In 1985, the Heckler report outlined the difference in health indicators between white and people of color, and honestly, things are worse now than they were in 1985. So, it's hard to talk about progress," Blount says.
Change clinical trial infrastructure
Blount suggests that one solution to addressing health disparities is to change the clinical trial infrastructure.
"Against the backdrop of last 40 years or so, more than $200 billion has been invested in research and community-based programs and philanthropy and all manner of ideas and efforts to achieve health equity, but we haven't gotten there yet," she says.
From the informed consent process to the location of clinical trials, the system is built against where and how black and brown people typically live. "Fundamentally, we've got a structure that doesn't comport itself to equity being accomplished," Blount says. "The way the systems of care are organized and delivered are not set up for black people, people of color or low-income people."
The number one reason people of color don't participate in clinical trials is not medical mistrust but that no doctor ever asks them, because doctors make assumptions about what black patients and Latino patients will and will not do, she adds. To participate in a clinical trial, you need to be near an academic medical center, you need to have time, money, childcare and transportation. That is not necessarily how patients are living.
Increasing the use of real-world studies can increase the enrollment of patients of color in clinical trials. These trials tend to accept nonmodel patients who are dealing with their condition in a very real life. "Real world studies are happening to a tiny degree now, but we need to conduct more so that we understand how these therapeutics work in the real lived experiences of people," Blount says.
Consequences need to be in place
Although the FDA has implemented the Enhance Equity Initiative to support efforts to advance diversity in clinical trials, there is no enforcement to encourage the practice. Some sort of consequences or incentives are needed in order to get researchers to try harder at achieving appropriate diversity in a clinical trial. Blount says this needs to be addressed through policy and enforcement. "The FDA says, 'we should have diversity in clinical trials,' but it doesn't enforce it," she says. "There are no repercussions for any researcher anywhere for not having appropriate diversity in a clinical trial. This needs to change because unfortunately, we just can't count on people to do things because it's the right thing to do."
Initiatives at the BWHI
The BWHI is doing its part with numerous initiatives, one of which is the Rare Disease Diversity Coalition (RDDC).
In May of 2020, BWHI launched the RDDC, to support rare disease patients of color facing racial disparities that created a serious health crisis for them. The RDDC was formed to identify and advocate for evidence-based solutions to alleviate the disproportionate burden a rare disease places on communities of color. The coalition brings together rare disease experts, health, and diversity advocates, and industry leaders to identify and advocate for evidenced-based solutions to alleviate the disproportionate burden of rare diseases on communities of color. Blount says this initiative has been successful because companies working in rare disease are usually smaller and more flexible and they were not afraid to have a conversation about medical bias and strive to be transparent about what they are doing to be inclusive in their trials. "We know black patients with a rare disease are waiting, on average, another five to six years longer to get a diagnosis than white patients," she says. "We've been able to fund groups to do proof of concept of the ideas that have come out of this coalition to see how they work so that we can then share that with hopefully, bigger Big Pharma, and researchers across the country.
Despite the slow movement in improving outcomes for patients of color, Blount says she believes achieving health equity for people of color is possible, but it will require change in behaviors, systems, policies and quality measures.
The pharmaceutical industry has yet to discover how nitrosamines occur in its drugs and how to mitigate the risk of that happening.
If you had bacon for breakfast, you may have ingested some nitrosamines, the organic compounds that were also found in Sanofi's Zantac and spurred a recall of the blockbuster heartburn treatment four years ago. The recall created an opportunity for legal action by patients who had been taking the drug, and the first court case is set to begin in February 2023 in California.
Consequently, the industry has been challenged with how to discover how nitrosamines occur in its drugs and how to mitigate the risk of that happening. The FDA has issued guidance on allowable amounts in drugs, and physician and patients look to find alternative treatment, if necessary. All three stakeholders are trying to assess the risk of getting cancer from the nitrosamines, and recent studies have shown the risk to be relatively low. According to the FDA, nitrosamines are common in water and foods, including cured and grilled meats, dairy products and vegetables. Everyone is exposed to some level of nitrosamines.
Zantac Trial Impact
In the case of Zantac, more than 3,100 plaintiffs have filed suits against Sanofi, claiming that the company didn't warn of the potential danger of nitrosamines in the drug. According to a recent Bloomberg report, the company is at risk of losing a ton of money; trial judgments against Sanofi could reach $45 billion. Sanofi has repeatedly denied any liability and analysts have stated they are doubtful the plaintiff's case has merit.
"Since 2019, the medical, scientific, and regulatory communities have extensively evaluated the safety of Zantac’s active ingredient ranitidine, and the data shows there is no evidence of consumer harm from real-world use of Zantac," Sanofi said in a recent press release.
In the Bloomberg report, George Gray, professor at George Washington University who specializes in health-related risk analysis, says, “It really is hard to say just how big the risk of these medications might be especially given the benefit they might confer on people.”
Sanofi's statement helped correct its stock price, which fell on the news of the lawsuit.
Both FDA and the European Medicines Agency evaluated the available data and found no evidence that Zantac causes cancer. FDA, in collaboration with regulatory counterparts around the world, has set internationally recognized acceptable daily intake limits for nitrosamines. If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate.
"Nitrosamine impurities may increase the risk of cancer if people are exposed to them above acceptable levels and over long periods of time, but a person taking a drug that contains nitrosamines at-or-below the acceptable daily intake limits every day for 70 years is not expected to have an increased risk of cancer," the FDA states.
Since the recalls and FDA's tightened regulation, the industry is still struggling with how to identify all the causes that create nitrosamine in medications and to prevent it from happening.
Where and when the impurities may occur is a complicated problem caused by numerable factors, ranging from something as straightforward as material used in blister packs to chemical interactions that occur before, during and after the drug making process.
Impact on physicians and patients
The FDA has offered guidance to physicians and patients, recommending physicians continue to prescribe medications when clinically appropriate and educate patients about alternative treatment options. Both pharmacists and prescribers may be able to dispense the same medication from a manufacturing lot that has not been recalled. Patients can find medications that have been recalled due to potential nitrosamine impurities on the FDA recalls webpage.
