This blog was written by Mark Manfredi, CEO of Kyn Therapeutics, as part of the From The Trenches feature of LifeSciVC.
“Time flies when you’re having fun.” That’s how I feel as I reflect on the first three years of the growth of Kyn Therapeutics. So much has happened since my R&D colleague Michelle Zhang and I moved into the seed space at Atlas Venture (see photo below of our cozy abode) to begin work on Kyn. As a first-time scientifically-trained biotech CEO, I assumed it would be similar to leading a project team in pharma – after all, the company started with only one asset! Turns out it’s more complex, and there have been many twists and turns along the way. While you can change focus from day-to-day, no area can be neglected, and don’t even think about choosing the wrong wine for a Board of Directors dinner.
A major component of our evolution at Kyn has been our transformation from a single asset company to an organization with three clinical and near clinical programs as well as a discovery pipeline. What were the triggers that have led us down this path? How did we decide to make this important move? What were the key elements that we believe have contributed to our successful growth? At Kyn we are still early in our company’s history, but I believe there are many relevant dynamics in our evolution to highlight. I share our story and thoughts below.
Once upon a time
At Kyn’s inception, IDO1 was all the rage. With almost two decades of preclinical validation and initial positive clinical data with epacadostat (IDO1 inhibitor from Incyte) there was a lot of investment in the pathway (e.g., BMS/Flexus, Genentech/NewLink). Our initial program was a biologics approach (engineered Kynureninase i.e. “Kynase”) that targeted both the IDO and TDO pathways and addressed a biologically relevant resistance mechanism of IDO1 selective inhibition (previous blog here). The program was still at an early stage in lead optimization when we started Kyn. Obviously the feeling around IDO1 selective inhibition has evolved since we started the company – more on that later.
Working on a single asset business model requires the dichotomy of belief that the project has the potential to change patients’ lives; with the understanding that generating key data has the potential to “kill” the opportunity. The challenge is to stay internally motivated knowing this and strive to convince investors to fund the idea while at the same time recruit new talent to join your fledgling company when the next experiment could be the end of the original thesis.
Navigating internal hiccups or changes in the external environment for a small company with a single asset is an art when you have a small team, limited cash, and ambitious investors.
Building the team that can evolve with you
The team you build drives your competitive advantage. There are many good people in biotech companies, but a highly functioning and effective team is more than just a collection of experienced people. Early hires are critical as they are a major factor in attracting future employees – talent begets talent, as well as being able to adapt and grow along with the company.
We initially hired seasoned senior executive-level scientists who brought both self-sufficiency and a significant amount of leadership in their discipline. The early senior hires helped shape projects and company strategy and build our consultant/CRO network. We began building an internal research team after a year in order to iterate faster and control costs for some of our critical discovery work, including in vivo experiments. This internal research team has been instrumental in the scientific and pipeline advancements Kyn has achieved to date. Since its inception, Kyn has delivered one program in Phase 1b/2, two additional assets proximal to the clinic, and a high- profile partnership with Celgene. And we did this with 14 full time team members continuing this semi-virtual model!
We supplemented our internal team with ex-large pharma consultants offering decades of valuable experience. We continue to choose those that not only provide a service but who are thought leaders in their discipline. Our consultants are an extension of our team and are empowered with decision making, invited to team building exercises, and are often onsite to mingle with the team. We make it a priority to keep them looped in at all times, not just when they are active on a project. This way, quick re-engagement when necessary is easy and seamless.
As Bruce Booth said in a 2012 blog post, “Make your board work for you.” This is a philosophy that’s served us well and has enabled our successful growth. Our board of directors comprises members with expertise in BD, financing, and R&D, and provide key connections with contacts within industry. Our close working relationship with the board and their willingness to get their hands dirty with us in every aspect of building the company has fostered a high degree of trust.
From one program to a pipeline
The collaborative relationship with the board was especially helpful when we weighed the decision to build beyond one pipeline project. Our internal team saw several opportunities that we wanted to act on. Based on insights from the kynurenine pathway of our initial project, we became excited about the idea of targeting the aryl hydrocarbon receptor (AHR) with a small-molecule antagonist. That project would become our first homegrown discovery effort. We also saw an opportunity to in-license a clinical asset (EP4 antagonist). These strategic shifts were big undertakings and we needed to build our case thoughtfully and with a lot of conviction. To present our case to the board and investors on why we wanted to target AHR, we developed a clear picture of the development path, asked what the POC trial would look like and “what is the likelihood for a biomarker driven sub-population?” We knew that if we couldn’t answer the first question, then maybe the clinical hypothesis was too early, even if the biology was cool (lesson learned from Raze Therapeutics – here). This process helped us to learn who we are as a company. While some enterprises choose to go with big biology and a longer lead time to a drug candidate – that’s just not us. Our argument gained board approval and investors trusted our team and the plan that we laid out.
Discovering AHR antagonists
AHR agonists demonstrated strong and broad immunosuppression and there is clinical proof-of-concept with a synthetic agonist tapinarof in psoriasis. Moreover, in cancer, many tumor types had high expression and activation of AHR. This evidence was the basis for developing an AHR antagonist to stimulate the immune system in cancer. We drove the project from initiation to development candidate in just 18 months and with approximately $6M in invested capital. We leveraged the internal and external team to run fast working on the critical cell/in vivo pharmacology and chemistry. Notably, we had an ace senior chemist doing compound design and leveraging a large medicinal chemistry team at a CRO and deeply experienced translational biologists to position the program for success in the clinic. Early efficacy work was done in a KOL’s lab, which helped bring external validation with the bulk of the pharmacology and translational work done internally. We will be the first AHR antagonist to enter the clinic in oncology later this year and in indications we selected based on biomarkers demonstrating AHR activation.
Bringing in the EP4 program
Another strategic decision we made was to in-license a clinical asset (EP4 antagonist). EP4 is a receptor within the COX-2 pathway which has strong association with poor disease outcome in cancer. While COX-2 inhibitors have yet to materialize as commercial therapeutics in oncology, clear clinical benefit has been seen in some patients. The field had evolved from targeting COX-2 for tumor intrinsic biology to the belief that this pathway was playing an immunosuppressive role through the receptors, most notably EP4. Also, there was a biomarker-driven approach with COX-2 expression and the metabolite PGE2 being associated with poor outcome in patients. We were able to leverage the experience of our board and particularly one of our investors who identified the asset through his network and helped with contract negotiation given his deep BD background. We assembled a clinical team quickly, leveraging consultants and internal clinical operations. Within nine months from in-licensing we were dosing our first patient with our EP4 antagonist (ARY-007) in a Phase 1b/2 oncology trial focused on two indications in the checkpoint resistant setting. This included making drug product, establishing a collaboration with Merck for Keytruda (free drug supply contract), and getting the clinical sites running. This catapulted us to a clinical staged company, which has had benefits beyond the program. We invested in clinical and translational capabilities and established KOL networks that have been leveraged for our earlier programs. It has also made the organization more mindful of clinical questions in early programs.
Financing a long-term leading oncology company
Building a “forever” biotech company takes sustainable capital and timing is everything. Unlike many larger companies, we are continually asking the question, “is this program financeable from an investor perspective?” New programs, emerging data from existing programs, and, importantly, external data can influence your thesis and your value proposition, for better or worse, as we found out last year.
In the spring of 2018, the ECHO-301 IDO trial data was made public: IDO1 inhibition added zero benefit to anti-PD1 treatment in melanoma. Though we had both data and strategy that significantly differentiated our kynureninase and AHR programs from IDO1 selective inhibition, the epacadostat phase 3 data cast a shadow over the pathway being therapeutically relevant in cancer. There is an existential question to be addressed when these events happen. The board met shortly after the readout and we all contributed to a healthy debate (no, really!). We could have shelved these programs but decided instead to stand by our science in this moment of industry doubt. And it paid off.
That summer, we began considering financing options with either a traditional series B or through a strategic partnership. Before embarking on an outreach campaign, we took the time to repackage our pitch to get ahead of the IDO story. Another piece of advice: scenario plan and optimize the message to the best of your ability. While we had the EP4 project (months from the clinic), the headwinds we hit with the outside investment community as a result of the ECHO-301 trial were significant. The industry as a whole was reeling from this study – not just for this pathway but for immuno-oncology in general. Most VCs (outside of our current investors) liked our story but some were hesitant to get into the “tainted” IDO space. They fell into two categories: those that heard we worked on the IDO pathway and decided immediately they were not interested; and others, more scientifically minded, who wanted to understand our differentiation.
On the partnering side, pharma had two decades of data supporting this pathway in oncology and believed in our package supporting our therapeutic differentiation from the IDO story. While external influences created some bumps in the road, we entered into a global strategic collaboration with Celgene on the Kynureninase and AHR antagonist programs. This brought in significant non-dilutive capital to fund these programs through phase 1b (with significant upside if successful) and the ability to further support our EP4 clinical asset and expand our pipeline with new discovery programs. This was transformative for us.
At Kyn, we are just getting started. We are committed to building a leading translational-driven oncology biotech company. I can’t say I know exactly where we will be five years from now, but I am confident that armed with a defined strategic plan, built on investments in the best intellectual capital and synergistic relationships, we will succeed in our endeavor to develop truly innovative cancer therapies while maintaining the open-mindedness and agility that has defined Kyn’s corporate philosophy since our inception.
The post Early Company Evolution – People, Pipeline, and Purse appeared first on LifeSciVC.
Avricore Health Signs Master Agreement to Pilot HEALTHTAB™ Platform For Diabetes Management in Select Shoppers Drug Mart® Pharmacies
Avricore Health (AVCR) announces that patients will soon have access to its innovative point-of-care blood screening and health-data management platform, HealthTab™…
“Next Level Dystopian Sh*t”: Amazon Rolls Out Portable Panic Booth For Warehouse Employees To Collect Themselves
"Next Level Dystopian Sh*t": Amazon Rolls Out Portable Panic Booth For Warehouse Employees To Collect Themselves
After years of reports of Amazon warehouse employees being forced to urinate in bottles, forego medical care, and work through…
After years of reports of Amazon warehouse employees being forced to urinate in bottles, forego medical care, and work through injuries - causing hundreds to launch petitions and revolt, the online retail giant has come up with a solution...
...a special sensory deprivation booth that allows stressed out employees to collect themselves before heading back out to the floor.
Known simply as the “ZenBooth,” the new apparatus, according to a video released by the company on Wednesday, is an “interactive kiosk where you can navigate through a library of mental health and mindful practices to recharge that internal battery.” -daily dot
Amazon's Leila Brown used her background in sports medicine and her passion in alternative therapies to create a space where our employees could focus on their mental well-being. https://t.co/bvk2bw9Lke pic.twitter.com/cEQhsTH0Od— Amazon News (@amazonnews) May 26, 2021
The "ZenBooth" is part of Amazon's WorkingWell program, which allows employees to "recharge and reenergize" with a series of "physical and mental activities, wellness exercises, and healthy eating support."
The panic booth features a small fan, some plants, and a library of meditation videos. Hopefully it features a toilet too.
(Did we mention most COVID-19 transmission occurs via aerosolized particles hanging in the air, particularly in poorly ventilated spaces?)
As the daily dot notes, the announcement received lots of pushback from Twitter users.
"why not just improve working conditions?" said one user.
"Or you could pay your employees well, not treat them like garbage, and accept unionization," added another.
"This is some next level dystopian shit. Maybe just pay people more and let them have bathroom breaks," read yet another tweet.
This is some next level dystopian shit. Maybe just pay people more and let them have bathroom breaks— katie ???? ???? (@Ah_occ_o) May 27, 2021
At least this is a step up from their now-abandoned, patented 'worker cages.'
Avricore Health’s CEO Discusses Abbott Diagnostics and Rapid COVID-19 Testing Rollout
Hector Bremner, CEO of Avricore Health Inc. (AVCR:CSE & AVCRF:OTC) Explains How HealthTab works with Abbott’s IDNow for Rapid COVID-19 testing
The following is an interview with Hector Bremner, CEO of Avricore Health Inc. (AVCR:CSE & AVCRF:OTC)
Avricore Health Inc. (AVCR) has been generating a lot of interest and excitement recently on the news of a partnership with U.S. health giant Abbott Laboratories and sizeable financings. In an exclusive interview, Avricore CEO Hector Bremner explains the upside at the Vancouver-based company.
Corona Stocks: Investors have zeroed in on your relationship with Abbott Diagnostics. Can you explain how you are well positioned to assist in Canada’s COVID-19 response?
Hector Bremner: For us it is huge. Abbott’s commitment to human health and point of care is by far second to none. Abbott is as equally focused on pharmacy as us and we have been really grateful to their team, we work quite closely right now and we think that relationship is going to mature over this year. Their device offerings have been fantastic and offer us the type of product offerings that we think fit pharmacy, particularly with the Afinion 2 which is the device that this quarter people will read and see a bit about from us. The Afinion 2 is a blood chemistry device, uses a very small sample, it is right there in the pharmacy. The test is conducted right there and it is screening for diabetes, conducting an A1C test and also testing lipids. So we think that the relationship with Abbott has been really tremendous. It is a really powerful partnership. We have this totally unique service that really brings the devices to life.
Corona Stocks: There was a disclosure that you are meeting with federal health officials along with Abbott and you are together seeking a federal government contract to create a platform using Abbott’s ID Now molecular testing device and Avicore’s HealthTab to test patients for COVID-19. The platform would use Avicore’s software to automatically report results from Abbott’s ID Now, presumably to government health authorities. Can you share any details on that?
Hector Bremner: We are actively pursuing conversations at all levels of government as we think HealthTab is missing piece to a truly successful rapid testing program and this is going very well. And, thankfully in the past few weeks, the focus of the conversation in the media and in government announcements has been moving positively towards rapid testing again. Up until very, very recently rapid testing has been seen as not as important as [getting vaccines]. Now everyone is stepping back and realizing that we are better off using these rapid tests as a way of getting a better line of sight as to what we are actually fighting, and quarantining, containing the virus into areas, really getting on top of it. You can’t fight something when you are in the dark.
Corona Stocks: What role would you play in this effort?
Hector Bremner: Fundamentally, we are a data generating and reporting platform, so that means using HealthTab to better track test results being done with rapid tests. There have several stories lately showing that much of the tests purchased by government have not been deployed. We are also hearing that tests are ending up on the black market. And, what is used, has created a lot of labor and questions about who and how to report this information to. So, HealthTab can automate a great deal of the labor and workflow and ensure timely disclosures and increase people’s confidence in these testing programs overall.
Corona Stocks: More testing will likely mean more cases, correct?
Hector Bremner: Yes, there was even a study this weekend that current estimates are that there are many times more cases than are ever announced at any time due to the lack of testing. We think rapid testing in 2021 and 2022 is going to play a critical role. And going forward for travel, and for certain workplaces and major events, having a real-time rapid reporting system in place to watch for virus outbreaks is something that is going to be part of the 21st century. This isn’t the first major virus outbreak over the last 20 years, it certainly has been the most impactful. We are seeing these viruses mutate very rapidly. The vaccine will get out there but we will be living with virus outbreaks. We have an incredible number of humans on the planet and they are very mobile and traveling all over the place, interacting with each other. The reality is we need to be very, very vigilant and we can’t let this happen again. Testing and real-time reporting is critical to this.
“Rapid testing, and having real-time reporting of [virus outbreaks], and breaking down the silos of communication, which is what HealthTab does, that is going to be critical to maintaining and avoiding future shutdowns.”
Corona Stocks: COVID-19 made for a crazy year for markets, but is a net positive for Avricore, correct?
Hector Bremner: It certainly opened up a business line that didn’t exist in the sense that viral testing – our platform is really fantastic for rapid response and getting real time eyes on the pandemic. We are still in those conversations and we are very bullish on where they are going. Canada in particular hasn’t been as progressive on the rapid testing front as other jurisdictions.
This said, we are making great strides in advancing our blood screening of diabetes and heart disease in pharmacy, and this demonstrates that while we can operate and succeed in today’s environment, we are going to excel beyond it.
Corona Stocks: It also seems given vaccine shortages becoming political dynamite, that governments are very motivated to be seen doing something positive?
Hector Bremner: I think so. We don’t want to do this again. This is a very costly endeavor and I am confident that the economy is going to rebound very quickly when we reopen and the fundamentals are still strong. But the reality is we got to this situation and after Bird Flu, Swine Flu, all of these outbreaks were contained and we were not vigilant, we were not taking them seriously. We need to ensure the infrastructure is there to monitor and respond quickly. We also need a healthcare approach of proactiveness. We offer an important tools in these efforts.
And it’s not just viruses, it’s the big costly killers like diabetes and heart disease that need more screening and monitoring. These issues are linked, and the expenses and deaths associated with them are avoidable. That’s our responsibility today, to act now and make tomorrow safer and healthier.
Corona Stocks: You already have Ontario pharmacy operators endorsing HealthTab, what support do you see coming from the health care industry this year?
Hector Bremner: Pharmacists recognize that they need to change their scope of practice. The future looks like point of care technology and cognitive services. We provide that platform so they are really leaning in on that. We know the patient has also made that decision. Good examples are 23andMe and Ancestry and health apps. With HealthTab and their community pharmacist, patients can take direct control and don’t have to spend huge amount so time to find out what they can now find out in minutes. They can walk in and learn if they have diabetes or if they already have it work with their pharmacists to manage it better. And the drug companies have already been going towards real-world evaluation and modifying the way they are doing studies to lower studies, which HealthTab facilitates in some really powerful ways.
All the players are making the decisions and right now the process is being adopted. Over the course of this year people are going to see from us that major pharmacy groups are really leaning in on the (HealthTab) system, they are going to be see drug makers and private players like insurance companies really leaning in on using our platform and trying to engage their customers better and also enhance their own operation.
Corona Stocks: Is there a competitor to HealthTab in the market?
Hector Bremner: Not directly, everybody is sort of adjacent to us. There are a million and one health dashboard apps, as I call them, that seek to be a digital interface for healthcare. But they are limited in terms of plug-ins and who can connect to them, which reduces their true effectiveness. There are also B2B enterprise solutions, and there are some device specific solutions, but again we are so successful is that we bring the patient, healthcare team, and researcher together by acting as a middleware, allowing for other technologies to be enhanced by the data we are able to generate and share.
So, our approach is entirely unique, and while someone else might have something similar, we have solved the shortcomings out there and will win the sector. It’s kind how Facebook overtook Myspace, both may seem similar, but won was just built better and put the focus on the user experience. That is what we are doing with HealthTab.
Corona Stocks: You are raising a lot of money, $3 million in the last few months. What is the reasoning behind that?
Hector Bremner: When you are running a public company, you are actually running two businesses as the same time. You are running the actual business where you are expected to be a subject matter expert and that is more than enough to fill your day. Then you have the market side of your business which is a whole other universe of activities. We did not want to head into this year, given our very full business development hopper, being split in our focus.
So late last year and into January-February we wanted to make sure we were fully capitalized, we will be debt free at the close of this current round and we will have sufficient capital to roll out what we plan to this year. As much of a dumpster fire that 2020 was, Avricore had a 10X year and we’re going to have another one. We think that we have got a lot of wind at our backs.
Corona Stocks: With your government background, coming to Avricore a year ago, it seems like the company is much more focused today on delivering the promise of HealthTab and playing a key role in fighting COVID-19.
Hector Bremner: My career has largely been in strategic communications and turning things around. We were no doubt in a tough situation when I first got involved, however we’ve done the hard work and sacrifices it takes to succeed and today, we are much more focused.
We fundamentally believe that all the sacrifices, all the hard work, were worth it because HealthTab is just that important. This team has done so much. Roger Seccombe, who developed HealthTab, our CTO, and everybody involved, they have all leaned in and made a lot of sacrifices, especially last year.
Today, we are getting to a place where other people are starting to now see it too and we are really excited. There are big things to come.
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