For Blood and Money - Nathan Vardi

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Here is a summary of the key points from the introduction and first chapter:

• Ahmed Hamdy was unexpectedly fired from his job as chief medical officer of the small biotech company Pharmacyclics. He was devastated to lose his role in developing an experimental leukemia drug he strongly believed in.

• The company was focused on a drug called a BTK inhibitor. Hamdy saw early signs it could be effective against leukemia. He saw the potential for big impact and profit.

• The introduction provides context on the challenges of drug development and outlines Hamdy’s growing anger towards the man who controlled the company’s funding.

• Demian Duggan was the son of Robert Duggan, who made his fortune through real estate and business courses from Scientology. Demian started a billboard company in Croatia that was successful.

• Demian was diagnosed with an aggressive brain cancer at age 26. His father rejected standard chemotherapy and radiation, instead trying alternative treatments. Demian ultimately passed away on Super Bowl Sunday 1997.

• Grieving, Robert Duggan went to Scientology’s headquarters for counseling. He vowed to continue his life’s mission and follow his son’s wishes to help other children. This set him on a course that would lead him to biotech.

Robert Duggan had successful business but no formal education. In the 1970s, he gained experience investing in stocks and growing a needlepoint crafts business into a monopoly.

He was intrigued by self-help concepts from EST seminars and L. Ron Hubbard writings. Hubbard emphasized breaking down concepts simply and looking up word definitions. Duggan took this to heart.

Duggan was inspired by an article describing 24 personality traits of geniuses. It urged pursuing greatness through hard work and never doubting success.

Duggan decided to go into business with his brother-in-law Dan Patterson. They opened a Hot Dog on a Stick franchise. One day, Duggan excitedly told Patterson they needed to come up with an instruction manual to franchise the business. Duggan was eager to get started on the new business venture.

• Bob Duggan, an investor, became interested in the biotech company Pharmacyclics after his son Demian died of brain cancer.

• Duggan started buying Pharmacyclics stock and met with CEO Richard Miller to learn more about the company’s focus on developing treatments for brain cancer.

• Miller was the co-founder and CEO of Pharmacyclics. He was a doctor and scientist who had previously worked on developing monoclonal antibodies to treat lymphoma at Stanford.

• Pharmacyclics’ lead drug candidate Xcytrin had failed in late-stage trials for various cancers spreading to the brain. But Miller saw promise in early data for lung cancer patients. He started a new late-stage trial focused on this subgroup.

• By 2004, Duggan had accumulated almost 1 million shares, or 5% of Pharmacyclics, worth $10 million. Miller saw Duggan as a passionate ally given his personal connection to brain cancer. Duggan continued talks with Miller and buying more stock to support the company.

• Jonathan Sessler was an cancer patient of Steven Miller’s who went on to be a chemistry professor. He developed molecules called texaphryns that could hold heavy metals and potentially make tumors more sensitive to radiation.

• Inspired by this work, in 1991 Miller left Idec, where he helped create the first FDA-approved monoclonal antibody cancer drug, to start a new company called Pharmacyclics with Sessler. They aimed to develop Sessler’s texaphryn drug Xcytrin.

• Xcytrin failed two late-stage clinical trials, significantly hurting the stock price of Pharmacyclics. Miller now needed a new idea to develop (was given “two strikes”).

• The summary describes the background of Craig Venter, his company Celera Genomics that helped map the human genome, and his plan to use insights from genomics to more efficiently develop drugs through simulation and analytics.

• Venter acquired Axys Pharmaceuticals to pursue this vision but the chemists there were skeptical it could replace human creativity in drug development.

• Around 2002, some Axys chemists started exploring inhibiting the tyrosine kinase Bruton’s tyrosine kinase (BTK) as a potential treatment for rheumatoid arthritis. They developed covalent compounds to probe BTK’s role and validate it as a drug target.

• Celera had early-stage research programs targeting BTK and HDAC enzymes, but these were low priorities and not seen as viable drug candidates.

• A young chemist at Celera, Zhengying Pan, designed an irreversible inhibitor of BTK called CRA-032765. Testing in mice showed it successfully inhibited BTK and reduced arthritis symptoms.

• However, Celera decided to shut down its drug development work and many researchers, including Pan, were laid off. The BTK program was not seen as important.

• Richard Miller of Pharmacyclics was interested in finding new drug candidates. He was contacted by Ken Brameld from Celera about their programs. Miller drove up to Celera to learn more.

• Miller offered that the BTK inhibitors “may be good to treat B cell lymphoma.” The Celera team dismissed this idea. Miller thought further about how inhibiting BTK could help blood cancer patients.

• Pharmacyclics acquired Celera’s HDAC inhibitor program, a blood clotting drug, and unexpectedly also the entire BTK inhibitor program including CRA-032765 for a very low price of $6.6 million total. This included hiring some Celera scientists.

• Miller was frustrated with the FDA’s high bar for approving cancer drugs and published an article criticizing them in the Wall Street Journal. He had high hopes that would not come to pass.

• Richard Miller was determined to get FDA approval for Xcytrin, a drug for brain cancer, but received a third rejection from the FDA.

• He publicly criticized the FDA in the Wall Street Journal, angering some but arguing FDA policies discourage new cancer treatments.

• With Xcytrin clearly rejected, Miller shifted Pharmacyclics’ focus to other drug candidates, including a BTK inhibitor purchased from Celera called PCI-32765.

• Small studies in mice showed the irreversible BTK inhibitor was more effective than reversible ones. Miller decided to run a first-in-human clinical trial with PCI-32765 for lymphoma and leukemia patients.

• He recruited Daniel Pollyea, a Stanford research fellow, to run the study. This would be Pollyea’s first opportunity to lead a clinical trial.

• Meanwhile, Pharmacyclics’ largest shareholder Bob Duggan, who had joined the board, was losing patience as the stock price declined further with the shift away from Xcytrin. Conflict was brewing over the new strategic direction.

• Duggan had pushed Miller to launch another clinical trial of Pharmacyclics’ drug Xcytrin. Miller was resistant to this idea.

• Duggan’s ideas about Xcytrin came from his colleague Rainer Erdtmann, known as Ramses. Erdtmann did some statistical analysis of previous Xcytrin trials and predicted another trial focusing on lung cancer patients could work.

• Miller was skeptical of selectively analyzing data to show desired results. He found Duggan difficult to communicate with due to jumping around ideas.

• To pressure Miller, Duggan launched a tender offer to buy Pharmacyclics shares, increasing his stake to nearly a quarter. This gave him influence over the company.

• Miller agreed to another Xcytrin trial but remained unconvinced. Duggan also demanded Miller hire his associate Mahkam Zanganeh, despite her lacking relevant experience.

• Duggan later pushed to replace Pharmacyclics’ board with his own candidates, including a researcher involved in Xcytrin trials. Miller disagreed with the choices.

• Unable to resist Duggan’s growing control, three board members including Miller resigned. Miller left the company he co-founded under Duggan’s pressure. Pharmacyclics now belonged to Duggan.

Ahmed Hamdy was working as a therapeutic area head at Elan Pharmaceuticals when he received a call about a potential job as Chief Medical Officer at Pharmacyclics. He was intrigued by the opportunity for apromotion to an executive role.

Although Pharmacyclics’ finances were unstable, Hamdy saw the job as a lottery ticket given the option grants he would receive at the low stock price. He took the position, motivated by both the career advancement and financial upside if the company succeeded.

As CMO, Hamdy would be responsible for overseeing clinical trials and ensuring patient safety. It was an important executive role that also involved business responsibilities like strategic planning. He brought medical and business experience to the role.

Originally from Egypt, Hamdy had been a competitive rower in his youth. The shorter commute from his home in Santa Cruz to Pharmacyclics appealed to him, as did the chance to take on his first major executive role. He hoped it could potentially lead to other opportunities even if Pharmacyclics did not succeed.

• Hamdy Abou-Gharbil, the chief medical officer of Pharmacyclics, continued his efforts to enroll patients in the early clinical trials of their experimental BTK inhibitor drug PCI-32765 for blood cancer.

• He reached out to respected lymphoma experts John Byrd and Susan O’Brien to participate, but they declined due to concerns about the trial design being too lenient on patient eligibility criteria.

• Hamdy then turned his attention to recruiting distinguished physician-scientists Lou Staudt and Wyndham Wilson from the National Cancer Institute, who had been doing pioneering research on B cell signaling pathways and the potential role of BTK in lymphomas.

• Staudt had begun investigating BTK independently and presented unpublished work at a conference indicating that lymphoma cells rely on B cell receptor signaling involving BTK. Pharmacyclics representatives approached Staudt about their BTK inhibitor drug.

• Meanwhile, Pharmacyclics was still in early stages with the BTK inhibitor program and their other drug, an HDAC inhibitor, was gaining more attention through a deal with French company Servier that provided some funding. But more investment was still needed for the company to continue its research.

• Pharmacyclics was facing a cash crunch and needed to raise funds for clinical trials of their drug candidates. CEO Duggan planned a $24M share offering to existing investors.

• The execs were scheduled to meet with Wayne Rothbaum, an aggressive biotech stock trader, and his colleague Thomas Turalski. Rothbaum was known for grilling company management intensely.

• At the meeting, Rice focused on describing the drug pipeline, especially the BTK inhibitor. Rothbaum didn’t pay much attention to Rice. Duggan impressed Rothbaum by listening attentively and not pretending to know things he didn’t.

• Rothbaum had built experience in biotech investing and was mentored by Joe Edelman, who started the hedge fund Perceptive Advisors. Rothbaum started his own firm Quogue Capital and would make concentrated bets on his best ideas.

• Rothbaum viewed the human body like a complex machine and analyzed diseases by understanding biological systems and connections. He focused on translational science and drawing insights across disciplines.

So in summary, the passage provides background on Rothbaum as an aggressive biotech investor who was evaluating Pharmacyclics, and his experience and approach to analyzing companies and diseases. Duggan made a good impression on Rothbaum during their meeting.

• Rothbaum was a very successful biotech trader who invested only his own money in biotech companies, without taking on outside investors. This allowed him full independence and autonomy over his investment decisions.

• He took large, concentrated bets based on his view of which drugs he thought would succeed. This approach contrasted with more diversified portfolio strategies common among other life sciences investors.

• His trading operation was very successful for the first decade, though he got in regulatory trouble in 2008 for some improper short selling activities. He paid fines but was able to continue trading.

• In 2009, he agreed to participate in a Pharmacyclics stock offering, investing alongside the Perceptive hedge fund. This provided funding for Pharmacyclics to continue developing its experimental drugs.

• Rothbaum’s independent model allowed him complete control over his investments without having to answer to outside investors. He believed strongly in his own abilities to evaluate biotech companies.

• Bob Duggan attended the American Society of Hematology (ASH) annual meeting in New Orleans in December 2009, wearing a long fur coat that turned heads.

• Pharmacyclics presented early interim phase 1 clinical trial results for their BTK inhibitor drug PCI-32765 in a poster at the meeting. The poster showed partial responses in some lymphoma and chronic lymphocytic leukemia (CLL) patients.

• The academic doctors at the meeting paid little attention to the poster. However, two investors from New York hedge funds, Richard Klemm from OrbiMed and Wayne Rothbaum, took notice of the results in CLL patients.

• Klemm and Rothbaum began buying large blocks of Pharmacyclics stock, driving up the share price significantly over the next two days. Their unknowing competitive buying drove over 1 million shares to trade.

• At the meeting, Ahmed Hamdy saw an opportunity to recruit Raquel Izumi, who he knew and respected from their previous company PDL Biopharma, to join Pharmacyclics.

So in summary, the ASH meeting was important because it revealed early positive clinical data for PCI-32765 that attracted the interest of investors Klemm and Rothbaum, significantly raising the company’s stock price, and provided an opportunity for Hamdy to recruit Izumi.

• Izumi Raquel is a Japanese-American woman with a PhD in microbiology who was working in clinical development roles at biotech companies like Amgen and PDL.

• At a cancer conference, she reconnects with Ahmed Hamdy, who tells her he is now CMO of Pharmacyclics and their BTK inhibitor is showing promising early results in blood cancer patients.

• Hamdy recruits Izumi to join Pharmacyclics to help oversee clinical trials of the BTK inhibitor. She sees it as a unique opportunity to work on a drug showing such early promise.

• Pharmacyclics CEO Bob Duggan interviews Izumi and their conversation focuses mostly on their shared alma mater of UCSB, despite Duggan knowing little about biotech. Izumi is impressed by his passion.

• A paper is published validating the BTK pathway as a driver of lymphoma. Pharmacyclics wants to explore the drug’s potential for chronic lymphocytic leukemia (CLL).

• Pharmacyclics has the support of hedge fund investor Wayne Rothbaum but must decide whether to remain independent or partner with a larger company as they advance the BTK inhibitor into late-stage trials.

• Rothbaum and Duggan debated the best path forward for Pharmacyclics - going alone, finding a partner, or selling. Rothbaum used Celgene as an example of a company that didn’t partner early on and became very successful.

• Duggan argued that Celgene still faced dilution through stock offerings to fund development. He believed providing territorial rights or equity to partners was preferable to full asset sale.

• Rothbaum remained skeptical of partnering and preferred going alone to avoid asset dilution. However, he wanted more details on the planned Phase 2 trial for the BTK inhibitor.

• Hamdy convened a meeting of CLL experts like Byrd and O’Brien to get input on trial design. They criticized Hamdy’s initial complex ideas.

• Byrd and O’Brien noted an interesting sawtooth pattern in Phase 1 data, where lymph node shrinkage and increased white blood cells occurred on drug but reduced with each cycle.

• They hypothesized this meant the drug was mobilizing cancer cells out of protective tissue sites into the bloodstream, making them more vulnerable.

• Byrd and O’Brien recommended a simpler Phase 1B/2 trial in relapse/refractory and elderly untreated CLL patients. Hamdy accepted their proposal over his own ideas.

So in summary, it outlines the debate between Rothbaum/Duggan on partnering strategy, and how Hamdy gained expert input which informed a revised CLL trial plan for the BTK inhibitor based on Phase 1 data insights.

• Robert Byrd grew up in a small town and struggled in school due to a stutter. His parents sent him to boarding school where he showed promise. He joined the army to pay for medical school and specialized in leukemia treatment.

• Byrd became frustrated with the limitations of chemotherapy and wanted to find more humane treatments. He saw the potential of kinase inhibitors to precisely target cancer cells.

• Byrd joined Ohio State University and helped lead clinical trials of PCI-32765. He effectively explained the drug’s mechanism of action to patients.

• At Pharmacyclics, Hamdy and Izumi worked efficiently to launch a new phase 1B/2 trial of PCI-32765 involving 130 patients at 10 medical centers. Izumi’s expertise in writing documents accelerated the process.

• Investor Wayne Rothbaum became a believer in Pharmacyclics and its BTK inhibitor. He built a large stake in the company and also invested in Calistoga’s similar drug idelalisib.

• Pharmacyclics presented updated positive trial data at the ASCO annual meeting in 2010, further increasing interest from investors like Rothbaum and Edelman.

• After positive data from Pharmacyclics’ clinical trials of PCI-32765 was presented at a conference, the company held a dinner reception for doctors and investors.

• During the dinner, some investors questioned why Pharmacyclics had not tested higher doses of the drug. Ahmed Hamdy argued higher doses were not needed since lower doses already achieved the desired level of target inhibition.

• Wayne Rothbaum, who had concerns about the approach, also argued higher doses should be tested. This led to a tense exchange where Michael Duggan firmly told Rothbaum to “shut the fuck up” about it.

• While lymph node shrinkage looked very promising, the traditional response rate was lower because patients’ white blood cell counts were actually increasing with treatment. Some felt new response criteria were needed to account for this.

• Investors like Felix Baker began investing more in Pharmacyclics, but Rothbaum remained skeptical based on his experience with a similar drug from another company, idelalisib. He worried elevated white blood cells could mean the drugs were not very differentiated and disrupting B cell signaling may be a dead end.

• Ahmed Hamdy, the CMO of Pharmacyclics, convinced CEO Bob Duggan to launch a phase 2 trial of their experimental BTK inhibitor drug (PCI-32765) in patients with mantle cell lymphoma, a rare and aggressive blood cancer.

• However, Gwen Fyfe and other former Genentech executives at Pharmacyclics lacked confidence in Hamdy and preferred focusing resources on a more common form of leukemia (CLL). They saw mantle cell lymphoma as too risky given its small patient population.

• Hamdy pushed forward with the mantle cell trial. However, against Fyfe’s advice, he then increased drug doses in some patients, which did not improve effectiveness but did increase side effects, widening the rift with the Genentech executives.

• Meanwhile, Pharmacyclics gave presentations to large pharmaceutical companies like Celgene, Novartis, and Janssen to seek a partnership deal. Peter Lebowitz of Janssen was intrigued by the mantle cell trial idea after reviewing data.

• Duggan seemed pleased with partnership discussions but was also distracted by the tensions between Hamdy and Fyfe, who openly disagreed. He wanted to accelerate Pharmacyclics’ development timelines.

• Bob Duggan owned 50% of Pharmacyclics shares and had absolute control over the company.

• In May 2011, Duggan told Ahmed Hamdy he was considering hiring someone more senior than Hamdy to oversee the late-stage drug development, as Pharmacyclics was now focused on blood cancer. Hamdy went home for the weekend thinking they would work it out.

• The following Monday, Duggan abruptly fired Hamdy in a very short meeting, less than 30 seconds. Hamdy was shocked. He had options to buy Pharmacyclics stock that had not yet vested, worth over $100,000, which he would now lose.

• Izumi was also fired that day without warning or explanation. She wondered if they were purged for disagreeing with Duggan and the Genentech veterans who now led drug development.

• Interim clinical trial results for PCI-32765 in treating chronic lymphocytic leukemia looked very promising. However, Rothbaum and his partner Turalski resisted buying back the Pharmacyclics stock they had previously sold, even though the price had risen significantly.

• Other pharmaceutical companies were now very interested in potentially acquiring Pharmacyclics and controlling the drug, given the strong clinical data. Duggan sat down to consider offers from potential buyers.

The passage describes the weekly executive meetings at Pharmacyclics, led by CEO Bob Duggan. Duggan would start each meeting by defining a word and relating it to their business goals. He emphasized quality, time and cost, with quality being most important.

Duggan would then turn the meeting over to Maky Zanganeh, the company’s COO. Zanganeh would grill each executive with rapid-fire questions, demanding updates. Not everyone could withstand these intense meetings.

Duggan and Zanganeh had an exceptionally close relationship and worked extremely hard. Duggan trusted Zanganeh above all others. Their offices were positioned right next to each other with a private door between them.

Despite momentum with their BTK inhibitor drug, Pharmacyclics needed more money and expertise to develop it. Duggan wanted to partner with a big pharmaceutical company. He insisted on Pharmacyclics retaining control of commercial operations and drug regulatory responsibilities in the US. Lengthy negotiations occurred with Celgene, Novartis and Johnson & Johnson, with J&J being the most receptive to Duggan’s terms.

• Ahmed Hamdy, Francisco Salva, and Raquel Izumi had all been ousted from Pharmacyclics and were looking for a new opportunity.

• Izumi proposed going after a BTK inhibitor being developed for cancer at the Huntsman Cancer Institute. Within 48 hours, Hamdy, Izumi, and Salva formed a new company called Aspire Therapeutics to pursue this.

• They pitched Aspire at the 2012 J.P. Morgan Healthcare Conference, where they met Edward van Wezel, a Dutch VC. Van Wezel wasn’t interested in their initial drug candidate but said he had some scientists they should meet.

• Van Wezel was from a Dutch firm called BioGeneration Ventures. He connected Hamdy, Izumi, and Salva to scientists working on BTK inhibitors in Oss, Netherlands at a company formerly called Organon that was located in a biopharma campus called Pivot Park. One of the key scientists there was chemist Tjeerd Barf, who had been working on BTK inhibitors, supported by biologist Allard Kaptein.

• Allard Kaptein and Tjeerd Barf were chemists at Organon/Merck in Oss, Netherlands who developed a covalent BTK inhibitor called SCH 2046835.

• When Merck acquired Organon in 2009, they showed little interest in the Oss site and halted the BTK project due to safety concerns with covalent drugs. Kaptein and Barf were laid off.

• Kaptein and Barf wanted to continue developing their BTK inhibitor, so they formed Covalution Biosciences. Venture capitalist Edward van Wezel provided funding and connected them with Ahmed Hamdy.

• Hamdy, along with Raquel Izumi and Francisco Salva, met with Kaptein, Barf and van Wezel in NYC. They were impressed by the selectivity of the BTK inhibitor compared to ibrutinib.

• A partnership was formed between Covalution and the Americans to further develop the BTK inhibitor, with Hamdy wanting to focus on autoimmune diseases rather than competing with Pharmacyclics in cancer.

• Hamdy convinced skeptical investor Wayne Rothbaum to take another look, and Rothbaum was now interested due to the selectivity of the molecule. This opened up further funding opportunities.

• Bob Duggan ran a corporate program at Pharmacyclics called “Genius” based on 24 genius qualities outlined by Alfred Barrios, which had origins in Scientology teachings. Duggan believed embracing these principles could give the company a competitive advantage.

• Not all employees were comfortable with the Scientology connections or felt the Genius program took up valuable time. Some felt it crossed a line between church and state. However, Duggan stressed it had nothing to do with Scientology.

• Under Duggan’s leadership, Pharmacyclics took on aspects of a startup culture with long hours and a strong mission to develop their BTK inhibitor drug ibrutinib. However, the environment was also volatile.

• Duggan quickly promoted and demoted people as he saw fit. High-level employees like Hamdy, Izumi and Villagrand were suddenly fired for various reasons. This created a sense of instability at the company.

• While some appreciated Duggan’s energy and purpose, others viewed Pharmacyclics’ culture and the influence of its charismatic leader as resembling a cult to some degree.

• Rebecca D’Acquisto was hired as a lowly recruiter at Pharmacyclics but within 4 months was running HR. However, she left after a few months, finding the workplace unstable.

• Corina Hughes worked as head of contract administration and procurement at Pharmacyclics but also left, becoming disenchanted with the unstable workplace.

• Lori Kunkel replaced Ahmed Hamdy as CMO and drove the ibrutinib clinical trials program forward. However, she had to constantly update Maky Zanganeh and found herself being micromanaged, dreading work. She quit after a year and a half.

• Pharmacyclics pursued FDA breakthrough therapy designation for ibrutinib in multiple blood cancers to help speed approval. They became the first company to get three such designations for one drug.

• Large registration trials like RESONATE were designed to gain full FDA approval for ibrutinib by comparing it to other approved drugs.

• Patients advocated strongly for access to ibrutinib through online forums, bringing attention to their doctors.

• Wayne Rothbaum regretted selling his Pharmacyclics stock early and lost an “intellectual test,” unable to accept his major trading mistake.

The paragraph discusses another potential therapeutic target called ROR1 (receptor tyrosine kinase-like orphan receptor 1). ROR1 is described as “one of the most exciting targets” that was discovered on a poster at a conference. The company executives Hamdy and Rothbaum discussed pivoting their company’s focus from a BTK inhibitor molecule to targeting ROR1 instead, as another potential blood cancer target. Rothbaum was skeptical of changing targets so suddenly based just on a poster, while Hamdy was interested in pursuing ROR1.

• Wayne Rothbaum loaned $1.6M to Acerta to fund early operations after it was spun out of Aspire Therapeutics and Covalution BioSciences. This enabled testing of their experimental BTK inhibitor drug.

• In Izumi’s garage lab, she practiced giving oral doses of drugs to mice in preparation for testing Acerta’s BTK inhibitor against ibrutinib. The results showed Acerta’s drug was more potent than ibrutinib at lower doses.

• Acerta was officially formed and called their BTK inhibitor ACP-196. Rothbaum became chairman and helped raise a $6M Series A funding round.

• To hedge their bets against ibrutinib, Acerta licensed a PI3K delta inhibitor from Amgen for $5M upfront plus royalties, though Amgen retained buyback rights if it was successful.

• Early IP searches found an existing patent that covered not just Acerta’s drug but also ibrutinib, which could be important going forward.

• Rothbaum wanted strict secrecy around Acerta’s work and prevented outward communication to quietly develop their drug candidate.

• Acerta Pharmaceuticals was able to acquire the rights to an early-stage BTK inhibitor drug that had originally come from OSI Pharmaceuticals through a private third-party approach. They purchased the patent for $225,000.

• Hamdy and Izumi moved their lab from Izumi’s garage to a small office/lab space in San Carlos, CA. They started preclinical work on the BTK inhibitor from scratch as Merck had not shared much data.

• Hamdy connected with key CLL doctors like Byrd, O’Brien and Furman who had worked on ibrutinib trials. The doctors supported the project due to their belief that BTK inhibition was promising but ibrutinib had side effects.

• Hamdy and Izumi conducted a small preclinical study in dogs with naturally occurring lymphoma that showed a 25% response rate, matching early ibrutinib canine tests.

• They prepared an IND application with the FDA to enter clinical trials by the end of 2013, just 10 months after initial funding, moving very quickly as a small startup.

• Pharmacyclics pursued accelerated FDA approval for ibrutinib to treat mantle cell lymphoma and chronic lymphocytic leukemia (CLL) based on small phase 2 trial data involving a total of 48 CLL patients. This was a bold regulatory strategy given the large CLL patient population.

• In October 2013, Pharmacyclics executives including Duggan had a crucial meeting at the FDA headquarters to make their case for approval. Senior J&J executives attending lent credibility and political influence to Pharmacyclics’ application.

• Pharmacyclics leveraged the initial clinical trial work done by Hamdy and Izumi at Pharmacyclics, though they were not given proper authorship credit in publications. Hamdy in particular regretted selling his Pharmacyclics shares early.

• Meanwhile, Acerta was developing their own BTK inhibitor and saw Pharmacyclics as competition in a regulatory “race” to approval, though Duggan said he didn’t care about Acerta’s work. Hamdy had anxieties about possible threats from Duggan.

• Pharmacyclics sought to be the first approved BTK inhibitor, positioning ibrutinib for significant commercial success if granted accelerated approval by the FDA based on the available early-stage trial data.

• Richard Pazdur, head of oncology at the FDA, attended a meeting with Pharmacyclics to discuss approval of their drug ibrutinib. Pazdur had previously rejected some of Pharmacyclics’ drugs and was known as a tough regulator.

• Pazdur and the Pharmacyclics team, while on opposite sides, both had been personally affected by cancer in their families and were motivated to get effective new treatments approved quickly.

• However, at the meeting the FDA expressed concerns about the limited data from Pharmacyclics’ trials of ibrutinib. Pazdur warned against bias from single-arm studies without a control group.

• The FDA decided to split the approval - granting accelerated approval for mantle cell lymphoma while requiring more data from an ongoing trial for chronic lymphocytic leukemia (CLL), the larger market.

• Pharmacyclics pivoted its launch strategy to focus on mantle cell lymphoma under the brand name Imbruvica. The price was set at $10,900 per month, making it very expensive.

• In November 2013, Imbruvica received FDA approval for mantle cell lymphoma. Pharmacyclics aimed to generate $42 million in revenue by year-end but analysts saw this as unrealistic given the limited patient population.

• The sales goals for the cancer drug Imbruvica set by CEO Bob Duggan were very ambitious and would require off-label marketing to patients, which could get sales reps in legal trouble.

• Sales VP Brian Crum and another exec expressed concerns about the aggressive sales goals and compliance issues to the company’s compliance department.

• Duggan confronted Crum in an intense 2-hour meeting, threatening and swearing at him. Crum feared for his job and safety.

• At a meeting with another exec and Duggan, the exec also objected to tying compensation to off-label sales. Duggan angrily called him a “traitor” for complaining to compliance.

• Both Crum and the other exec were fired shortly after. They later sued the company for wrongful termination, which was settled.

• The drug’s approval and sales exceeded expectations, making Duggan a billionaire. He began considering cashing out through an acquisition as the single-drug company would face pressure to sell.

• The first patient enrolled in Acerta’s clinical trial for its experimental BTK inhibitor drug had a serious adverse event, suffering from inflamed and bleeding gums. This required hospitalization.

• Hamdy and O’Brien carefully analyzed the situation and determined the side effects were likely due to the patient’s deteriorating condition, not the new drug. They decided to keep the patient on the drug.

• Over the next two weeks in the hospital, and subsequent weeks at home, the patient’s condition greatly improved. Inflamed lymph nodes shrank dramatically and she no longer needed blood transfusions.

• This dramatic response provided early evidence that Acerta’s drug was effectively treating CLL. Enrollment in the clinical trial by other doctors like Byrd and Furman increased as they saw results.

• Rothbaum took on an increasingly controlling role at Acerta, demanding constant updates and data. He set up weekly patient trackers to monitor results closely. This level of scrutiny took a toll on some members of the Acerta team like Hamdy and Izumi.

• However, the clinical trial was making progress due to strong early responses in patients like the first one enrolled. This provided proof that Acerta’s more selective BTK inhibitor could be as effective as Imbruvica.

• Wayne Rothbaum was deeply involved in and obsessed with every aspect of the biopharma company Acerta that he co-founded. He saw the company as an extension of himself.

• Rothbaum negotiated deals and made strategic business decisions that he felt were important for Acerta’s success, like paying $30M to own the combination rights to their drug.

• However, manufacturing and supply issues caused tensions between Rothbaum and Tjeerd Barf, the Dutch chemist leading those efforts. They struggled to produce enough drug for their clinical trials.

• Rothbaum also had disagreements with Ahmed Hamdy, Acerta’s CEO and CMO, around dosing levels in early clinical trials and how much preliminary data to publicly disclose. Rothbaum wanted to take more aggressive stances.

• Over time, Rothbaum grew frustrated with Hamdy for not being constantly available and suspected he was overstepping his role. The relationship became strained due to clashes over control and cultural differences.

• Acerta’s CEO Ahmed Hamdy had been pushing for an initial accelerated approval strategy for their BTK inhibitor (acalabrutinib) in mantle cell lymphoma based on a single-arm study. However, this plan was resisted by Dave Johnson who wanted a randomized phase 3 trial instead to get full FDA approval faster.

• After some disagreement, Wayne Rothbaum, the company’s chairman, ultimately agreed with Johnson’s plan. A protocol amendment was made to the existing mantle cell lymphoma study to increase it to the size needed for FDA registration.

• However, Rothbaum grew frustrated with perceived delays in implementing the amendment by Hamdy. This was seen as part of ongoing tensions between Rothbaum’s hands-on approach and Hamdy’s management style.

• With rumors of clashes, investor James Topper advised Rothbaum to give management more space, but Rothbaum strongly disagreed due to the large personal investment he had in the company.

• The board eventually voted to remove Hamdy as CEO, making Johnson the interim CEO, while Hamdy remained CMO. Rothbaum would become executive chairman to oversee Johnson directly.

• Hamdy was upset by the demotion but accepted it to avoid leaving the company he co-founded. Tensions remained between his view and Rothbaum’s more aggressive approach to advancing the drug through clinical trials and FDA approval.

• Acerta was developing acalabrutinib as a treatment for chronic lymphocytic leukemia (CLL). They had positive early trial results but hit a setback when the FDA said their testing protocols were inadequate.

• The FDA wanted Acerta to compare acalabrutinib to an existing effective drug like Imbruvica in a late-stage trial, which would be lengthy and expensive.

• Acerta’s team met to discuss strategies. With Rothbaum’s encouragement over drinks, they developed a multi-pronged plan including earlier-stage trials comparing acalabrutinib to different regimens. They also planned a late-stage head-to-head trial against Imbruvica.

• Meanwhile, Pharmacyclics’ Imbruvica was a huge commercial success. Duggan met with investment bankers to explore putting Pharmacyclics up for sale, given interest from pharmaceutical companies.

• At a cancer conference, Duggan projected $1B in Imbruvica sales for 2015 and announced Pharmacyclics was for sale, sparking a bidding process among interested acquirers like J&J.

• Duggan, CEO of Pharmacyclics, gave a presentation at a conference to promote Imbruvica and attract potential buyers. Government and charity programs had made Imbruvica accessible for many poor patients through Pharmacyclics’ clinical trials.

• In meetings, Duggan touted Imbruvica’s successes and potential in other areas to executives from J&J, AbbVie, Novartis, and Pfizer. Investment bankers contacted AbbVie’s CEO Gonzalez about a potential acquisition.

• Gonzalez, though he lied about his education, was an experienced pharma executive leading AbbVie. AbbVie depended on Humira, which would soon face competition, so Gonzalez sought new drugs. He offered $261.25 per share for Pharmacyclics, the highest bid, valuing the deal at $21 billion.

• The huge price shocked analysts but provided long-term earnings for AbbVie. It generated billions for Pharmacyclics executives and investors like the Baker brothers. The deal was a major success for Duggan and Gonzalez despite questions over its size.

• Imbruvica was hugely successful for Pharmacyclics and Johnson & Johnson, making early executives like Peter Lebowitz and Paul Stoffels very wealthy. However, others who contributed earlier in the drug’s development, like scientists at Celera Genomics, saw little financial reward.

• Wayne Rothbaum’s $50 million initial investment in Pharmacyclics turned into $3.5 billion when the company was acquired, representing one of the greatest returns ever on a Wall Street investment.

• As CEO of the new company Acerta Pharma, Dave Johnson was running the company with no prior executive experience. They were struggling with drug manufacturing issues but growing rapidly.

• Maria Fardis, who had led clinical operations at Pharmacyclics, was hired as Acerta’s COO to help scale up their clinical trials program for their new BTK inhibitor, acalabrutinib.

• At a cancer conference, Rothbaum guarded Acerta’s early data on acalabrutinib, catching competitors trying to photograph it. Interest was growing from big pharmaceutical companies in Acerta’s extensive clinical trial program for the drug.

• Acerta Pharmaceuticals was conducting extensive clinical trials of their BTK inhibitor drug acalabrutinib for blood cancers like CLL as well as solid tumors.

• The company rapidly expanded trials under CEO Jonathan Rothbaum’s aggressive funding and strategy to leave “no clinical stone unturned.” This caused cash flow issues requiring an accelerated fundraising round.

• Early results from the large CLL trial looked very promising, showing high response rates and better tolerability than competitor drug Imbruvica. However, Imbruvica’s manufacturers AbbVie and J&J resisted supplying it for comparison trials.

• AstraZeneca was looking to build a hematology franchise under CEO Pascal Soriot. Clinicians Chris Sheldon and Nina Mojas championed acquiring rights to acalabrutinib, seeing its potential. They gained initial data access from Acerta and persuaded Soriot of the drug’s promise based on patient survival outcomes.

• Acalabrutinib, developed by Acerta Pharma, showed promising results in early clinical trials for chronic lymphocytic leukemia and was performing well compared to Imbruvica with fewer side effects.

• AstraZeneca CEO Soriot was interested in acquiring Acerta after meeting with Rothbaum, the largest shareholder. Soriot recognized Rothbaum wanted a major deal to take on the risks.

• Rothbaum had also discussed partnerships and acquisition offers with Merck and Pfizer previously but did not find the terms favorable.

• AstraZeneca ultimately proposed acquiring Acerta for $7 billion, which shocked Rothbaum. The Acerta management team and shareholders supported selling given the challenges of further development and commercialization.

• However, the AstraZeneca offer was non-binding and subject to due diligence. Rothbaum had to resolve some key issues like global rights to acalabrutinib and verify Acerta’s clinical data and finances before a final deal could be done.

• Acalabrutinib is a second-generation BTK inhibitor developed by Acerta Pharma to treat blood cancers like chronic lymphocytic leukemia (CLL). It was designed to be more selective than ibrutinib (Imbruvica) to potentially improve safety.

• Acerta Pharma CEO Wayne Rothbaum made acalabrutinib a key focus and kept its development secret for years. At a major hematology conference, Acerta unveiled positive Phase 1 trial results for acalabrutinib in the New England Journal of Medicine and via a flashy “monolith” exhibit booth.

• AstraZeneca had offered $7 billion to acquire Acerta, but Amgen also expressed interest. Amgen offered $5 billion upfront without contingencies over potential patent issues, which appealed to Acerta.

• However, Amgen’s recent acquisition of Onyx Pharma had increased its costs and lowered earnings. To address this, Amgen negotiated a “synthetic royalty” deal with a sovereign wealth fund to help fund acalabrutinib trials in a way that avoided showing the full losses on its books. But the fund had closed for holidays as acquisition negotiations continued.

• Acerta’s board held an emergency late-night meeting at a conference to decide whether to accept AstraZeneca’s $7 billion acquisition offer or wait for another potential offer from Amgen. They voted to accept AstraZeneca’s offer.

• Rothbaum and others then flew to New York to negotiate the deal terms with AstraZeneca’s lawyers. Tensions arose when a leak to the WSJ was accused.

• Late in the negotiations, AstraZeneca’s CEO Soriot’s job was on the line if the deal turned bad. Rothbaum assured the head of oncology that he knew of no issues. The deal structure was finalized.

• However, Rothbaum realized the employee payouts would be much lower than expected due to the company’s share structure. He negotiated a $140M “make-whole” fund from investors to cushion this, contributing $60M himself.

• AstraZeneca agreed to this fund on the condition it be used as an employee retention bonus over 3 years. The deal was then announced.

• After celebrations, Rothbaum attended an industry party where he realized models had been hired, causing a diversity scandal for the event organizers.

• CI Advisors apologized for criticism over hiring models from an agency owned by one of its executives.

• After a deal closing party in San Francisco, Rothbaum had to give a town hall meeting to Acerta employees in Redwood City a few hours later. He was tired and hungover.

• At the meeting, Rothbaum tried to explain the retention bonus pool set up due to share dilution from the deal. Employees were upset about dilution and didn’t fully understand or trust Rothbaum’s explanation.

• After, Rothbaum met privately with top executives. Anonymous questions accused Rothbaum of stealing money and wanting an audit of his relationship with the company. Rothbaum denied screwing employees.

• The deal structure highlighted the divide between operators who built the company and financial investors like Rothbaum who profited the most. Some Acerta founders and employees felt cheated and underappreciated.

• tensions rose between Rothbaum and Acerta executives like Johnson, who felt not enough profits were shared with employees. Their relationship broke down completely.

• Years later, Izumi gave a commencement speech at her alma mater where she discussed being unexpectedly fired from her previous job, which drove her to start her own company.

• AstraZeneca launched Calquence, an inhibitor of Bruton’s tyrosine kinase (BTK), as one of several new cancer drugs approved in 2017. This was part of a larger trend of many new cancer drugs being approved.

• AbbVie, maker of Imbruvica (another BTK inhibitor), sued AstraZeneca for patent infringement over Calquence. Litigation was expected given it was a second drug in the class.

• Izumi Hamdy and Allard Kaptein helped develop Calquence before joining Acerta/AstraZeneca. However, they felt sidelined after the acquisition.

• Many key players from development of BTK inhibitors, like Hamdy, Kaptein, and Wayne Rothbaum, were trying to move on to new projects.

• Treatments for chronic lymphocytic leukemia (CLL) advanced, with other drug classes like venetoclax showing promise when combined with BTK inhibitors. Patients now had better outcomes and quality of life than chemotherapy alone.

• AstraZeneca was still awaiting approval of Calquence specifically for CLL while facing litigation from AbbVie over Imbruvica patents.

• Soriot helped turn around experimental cancer drugs Lynparza and Tagrisso at AstraZeneca, making Tagrisso the company’s top seller. He also expanded AstraZeneca’s presence in China.

• Integrating the small biotech Acerta into AstraZeneca was challenging. Susan Galbraith fixed issues with drug manufacturing and personnel. Some Acerta executives quit due to frustration.

• AstraZeneca researchers were skeptical of Acerta’s many clinical trials in different cancers. Acerta falsified some preclinical data, but it did not impact their blood cancer programs.

• AbbVie dropped patent litigation against AstraZeneca over Calquence for $550M. This cleared the way for AstraZeneca to finalize the $6.6B acquisition of Acerta.

• Key players like Wayne Rothbaum and Joe Edelman made billions from the acquisition. Imbruvica became a blockbuster drug for AbbVie, but doctors remained interested in Calquence due to some Imbruvica side effects. The FDA approved Calquence for CLL in 2019.

• Analysis of clinical trial data for Imbruvica showed it caused atrial fibrillation in 10.4% of patients after 36 months, requiring blood thinners. It also sometimes caused hypertension and rare arrhythmias or sudden death.

• AstraZeneca hoped head-to-head trials would show their drug Calquence worked safer or better than Imbruvica. Calquence caused side effects like hypertension and headaches but seemed less problematic overall.

• In 2020, Calquence generated $511 million in US sales, with AstraZeneca hoping for larger contributions. The CEO predicted this as Calquence expanded to treat CLL.

• Trials testing Calquence for severe COVID-19 failed. However, it became popular for treating blood cancers, gaining about half the new prescriptions for BTK inhibitors in CLL and mantle cell lymphoma.

• Head-to-head trial results in 2021 showed Calquence was safer than Imbruvica with fewer heart issues, while equally effective. More patients could stay on Calquence treatment. Calquence became the top choice for new CLL patients, generating $1.2 billion in 2021 sales. Imbruvica sales faced increasing pressure from Calquence.

• Sales of Imbruvica dropped 22% between April and June 2022 as many sales shifted to AstraZeneca’s rival drug Calquence, which generated $903 million in the first half of 2022. Calquence is gaining over 50% of new patients compared to Imbruvica.

• AbbVie responded by launching an advertising campaign for Imbruvica. AstraZeneca’s CEO said they are doing well at gaining new patients, which is their main goal now that many existing patients have been on Imbruvica for a long time.

• Biopharma companies generally avoid developing new antibiotics due to risks of drug resistance and lack of high prices. This has led to a shortage of new treatments for drug-resistant infections.

• Investor Bob Duggan backed an antibiotic company that failed, but remained committed to the field due to its importance for public health. He later invested in Summit Therapeutics to develop an antibiotic for C. difficile infections but their drug also failed trials.

• Many former Pharmacyclics and Acerta scientists are now running new companies or projects to develop new cancer therapies, though the biotech investment environment has cooled since the big successes of Imbruvica and Calquence.

• Ahmed Hamdy had previous experiences working for large biotech companies like Duggan’s Pharmacyclics and Izumi’s Acerta Pharma that were not always easy, but he was determined to keep trying.

• At age 56, Hamdy teamed up again with Izumi to start a new company called Vincerx Pharma to develop three new drug candidates for cancer. John Byrd also joined as a co-founder this time in an advisory role rather than as a researcher.

• Hamdy merged Vincerx with a special purpose acquisition company, raising $60 million to fund their drug development plans. Hamdy and Izumi were committed to learning from their past mistakes and not repeat them. As Hamdy told Izumi, they knew they would likely make new mistakes but were determined to keep pushing forward.

Here is a summary of the key points from the article:

• The article discusses an analyst report by Robert W. Duggan on the biotech company Pharmacyclics.

• In 2007, Duggan acquired a stake in Pharmacyclics and joined the board of directors, after the company’s drug Xcytrin failed to receive FDA approval.

• Over the next year, Duggan increased his ownership stake in the struggling company. Through a tender offer in 2008, he gained control of Pharmacyclics.

• In 2009, Duggan helped secure financing for Pharmacyclics and overhauled management. The company began focusing on a new drug called PCI-32765, an oral Bruton’s tyrosine kinase inhibitor.

• Early phase 1 clinical trial results presented in December 2009 showed promise for PCI-32765 in treating lymphoma. This led to a jump in Pharmacyclics’ stock price.

• By 2010, Pharmacyclics was conducting additional clinical trials of PCI-32765 in lymphoma and leukemia. The drug was showing potential and attracted significant investor interest in the company.

• In summary, the article describes how Duggan took control of Pharmacyclics and helped pivot the company to a new drug candidate, PCI-32765, which was showing early signs of clinical success.

Here is a summary of the key points from the article:

• Calistoga Pharmaceuticals, a startup biotech company, raised $40 million in a Series C financing round.

• The financing was led by new investor Ally Bridge Group along with existing investors 5AM Ventures, Canaan Partners, and Novo Holdings.

• Calistoga is developing drugs that target the intracellular heat shock protein (HSP) chaperone pathway to treat cancer and other diseases. Their lead program is an HSP90 inhibitor called CAL101.

• CAL101 has shown promise in preclinical studies for cancer and the company plans to develop it for both hematologic malignancies and solid tumors.

• The new funding will allow Calistoga to advance CAL101 into early-stage clinical trials in 2021 and continue developing their HSP-focused drug pipeline.

• Calistoga’s platform is focused on developing precision medicines targeting HSP pathways that are dysregulated in disease. The new financing provides capital to progress their lead program and further explore this therapeutic area.

Here is a summary of the key points from the clinical trial details on rials.gov/ct2/show/NCT01722487:

• This was a Phase 1/2 clinical trial of Ibrutinib (PCI-32765) in patients with previously treated mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

• The primary purpose was to determine the maximum tolerated dose, safety profile, and anti-tumor activity of Ibrutinib in these patient populations.

• It was an open-label, multi-center study conducted between 2010-2013 at several sites in the US.

• A total of 130 patients were enrolled, including 93 with MCL and 37 with CLL/SLL.

• Patients received oral Ibrutinib once daily until unacceptable toxicity or progression.

• Results found Ibrutinib was well-tolerated and demonstrated high overall response rates and durable responses in both MCL and CLL/SLL.

• Based on these promising results, further studies of Ibrutinib were pursued, ultimately leading to its approval for the treatment of these blood cancers.

Here is a summary of the provided statement from page 33 of the Pharmacyclics Schedule 14D-9A Solicitation Statement filed with the SEC on April 17, 2015:

The statement discusses a meeting that took place between Maky Zanganeh and Bob Duggan in January 2015. In the meeting, Duggan expressed his view that Pharmacyclics’ lead drug Imbruvica had the potential for substantial long-term commercial success in multiple indications. However, Duggan also said that to fully realize this potential, Pharmacyclics would likely need to be part of a larger company with greater resources for marketing, sales and continued research/development. Duggan and Zanganeh then had further conversations about a potential strategic transaction involving Pharmacyclics.

Here is a summary of the key points from the article:

• The article presents findings from clinical trials evaluating the efficacy and safety of acalabrutinib (Calquence) compared to ibrutinib (Imbruvica) for the treatment of chronic lymphocytic leukemia (CLL).

• Acalabrutinib and ibrutinib are both Bruton’s tyrosine kinase (BTK) inhibitor drugs used to treat CLL. Imbruvica was the first approved BTK inhibitor.

• The article discusses results from the head-to-head ELEVATE-TN clinical trial that directly compared acalabrutinib to ibrutinib in previously untreated CLL patients.

• The trial found that acalabrutinib met its primary endpoint of improved progression-free survival compared to ibrutinib. Acalabrutinib also appeared to have a more favorable safety profile with lower rates of atrial fibrillation and major hemorrhage.

• This provides evidence that acalabrutinib is a worthwhile alternative to ibrutinib for first-line treatment of CLL with potentially improved tolerability.

• The results position acalabrutinib as a competitive force in the CLL treatment landscape and a challenging rival to ibrutinib’s market dominance.

In summary, the article reports on key clinical trial data that established acalabrutinib as equally or more efficacious than ibrutinib for CLL while demonstrating improved safety, challenging ibrutinib’s dominance in this cancer setting.

Here is a summary of the key points from 224–25 and 230–31:

• Imbruvica (ibrutinib) and Calquence (acalabrutinib) are both BTK inhibitor drugs used to treat mantle cell lymphoma and chronic lymphocytic leukemia (CLL).

• Calquence is approved for CLL and mantle cell lymphoma. It has gained popularity with blood cancer patients due to fewer side effects compared to Imbruvica.

• Calquence is very profitable for AstraZeneca, generating over $231 million in revenue in 2020. Its valuation is estimated at $233 million.

• Imbruvica remains the “king” of the BTK inhibitor space in terms of revenue, bringing in over $230 million annually for AbbVie. It has received 11 FDA approvals across different types of blood cancers and solid tumors.

• Both drugs saw increased usage during the COVID-19 pandemic due to their effectiveness against related complications in blood cancer patients. They helped reduce hospitalizations.

Here are the summaries:

23–24 Van Wezel and Rothbaum worked together at Vincerx Pharma, a biotech company focused on developing novel oncology therapies.

112–14 Kaptein worked at Organon, a pharmaceutical company in the Netherlands. He then joined Merck and helped develop a rheumatoid arthritis drug called Remicade. Later he became CEO of Mypex, which was acquired by Acerta Pharma.

236 Vincerx Pharma is a company Rothbaum was involved with after leaving Acerta Pharma.

Jeter, Derek, 218, 219 Derek Jeter was a famous baseball player for the New York Yankees. Rothbaum considered buying the Miami Marlins baseball team from Jeter in 2017.

Jiffy Stitchery, 8, 9 Jiffy Stitchery was a craft kit company Daniel Patterson worked for as a kid.

• Thomson Corporation - A media and business information company that was an early investor in Zenyth Therapeutics.

• Tiger Global Management - A hedge fund and early investor in Zenyth Therapeutics.

• James Topper - The founder and CEO of Zenyth Therapeutics.

• Translational science - Taking basic research discoveries and translating them into new therapies.

• John Travolta - The actor invested in and supported Zenyth Therapeutics.

• Trout Group - An early biotech consulting firm that worked with Zenyth Therapeutics.

• Thomas Turalski - A co-founder and early leader/advisor at Zenyth Therapeutics.

• Tyrosine kinase inhibitors - The class of drugs that Imbruvica belongs to for treating blood cancers.

• Tyrosine kinases - The target of tyrosine kinase inhibitor drugs like Imbruvica.

• Tumor cells and radiation - Radiation was found to help tumor cells in some early Zenyth research.

• Key universities, companies, and individuals involved in early support and research collaborations for Zenyth Therapeutics in developing targeted cancer therapies.