When the Target Isn’t Really the Target: One Way Cancer Drugs Fall Out of Clinical Trials

RICKI LEWIS | October 24, 2019 | 159 views

Ninety-seven percent of potential new cancer drugs never make it to market, dropping out of clinical trials when they don’t meet measures of safety or efficacy. “Why that is, we don’t really know. But I think that this extremely high failure rate suggests that there are some fundamental issues in how new drug targets are studied and how new drugs are characterized,” said molecular biologist Jason Sheltzer, PhD, an Independent Fellow at the Cold Spring Harbor Laboratory on Long Island, NY. He decided to investigate, and uncovered the potential power of publishing negative evidence. The work fits in with Open Access week here at Public Library of Science. CRISPR Improves Precision. The team reports in Science Translational Medicine on using the gene editing tool CRISPR-Cas9 to test whether 10 experimental cancer drugs work exactly how their developers predicted they would. And they found a tunnel vision in the way that drugs are targeted that might explain why certain patients do not respond as hoped.

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Why Is Diversity of Thought Essential for Developing a Winning Strategy?

Article | April 17, 2020

In developing or evolving a strategy, there are key decision moments. Those are the moments where you are deciding where you need to focus, what you need to excel at to win there, and where and how to allocate resources to get to a point in the future. At these moments, it is the contest of ideas that matters. Having choices matters. Having a cross-functional team participating in the development of strategy is one way of ensuring that you are going to be more successful at generating choices before you start making choices. What Is a Cross-functional Team? A cross-functional team is a collection of individuals with varied skillsets from different areas of a business collaborating to achieve a common goal. Why Are Cross-functional Teams Essential for Business Success? Having this diverse set of minds analysing the situation, considering the big picture and the organisation’s capabilities, and the needs of all stakeholders, inspires teams to think about the choices they have differently and more creatively. For example, in a pharmaceutical setting, the medical affairs team brings knowledge of the data, unmet needs, and insight into clinical practice. Access and reimbursement teams identify the right data and take the lead in building that value story to accelerate market access and product uptake. It is incumbent upon commercial to hear their ideas, obtain their perspective and secure their alignment to all strategy decisions. Cross-functional collaboration can help break down silos. Research suggests that working in silos and not sharing data with team members from other departments can cost a company close to $8,000 per day in wasteful expenses. Time is widely recognised as a scarce resource: we need quick access to accurate and real-time insights to make effective business decisions. Real time insight will come from those closest to the customer, so it is important for cross-functional members from different geographies to participate in the development of strategy. Improved insight is a source of sustainable competitive advantage. One single version of the truth is what is required for the right narrative to take place. The right narrative will lead to the right decisions. One single version of the truth is more easily achieved by cross-functional team members working closely together. Better Innovation & Creativity: Individuals with diverse skillsets often explore a problem in different ways. When different people working in different capacities come together, they think outside the box to significantly improve outcomes. It is a great way to come up with concepts that distinguish companies from their competitors. Achieving alignment with strategy across functions and geographies: Today, businesses are moving faster than ever and organisations are seeing possible competitors in areas they never knew existed before. With so much choice about where to focus, you really want your workforce to align around one strategy. Underperformance is inevitable if everybody is off working in ten different directions. Improving the customer experience: Creating an effective customer experience is about more than just ensuring your customers receive the products and services they desire in a timely and efficient manner. It’s also about creating touchpoints with real people who can organically evangelise and grow your brand through their social media and offline interactions with friends and family. Your customers are engaging with multiple communication channels– official websites, social platforms, virtual platforms, medical science liaisons, sales reps, and more. Everyone needs to be aware of, and understand, the moments that matter to your customer and the business along that customer journey and how they contribute to delivering that positive experience. This is more likely to be achieved with a cross-functional approach to strategy development. Business Agility: Cross-functional teams are typically small, adaptable, and flexible. Such teams can move faster as they don’t have to wait and rely on other departments or external sources. They can help in tackling any silo mentality and bridge gaps between team members. They can come together to consider new information and/or changes to adapt the strategy if necessary and/or react to any setbacks immediately. They are better placed to make decisions when problem-solving amidst uncertainty. In summary, the rapidly changing environment and new information requires medical affairs, along with access and reimbursement and commercial, to work together, to ensure that patient’s benefit from the value of new innovative therapies. Companies stand a better chance of creating a winning strategy if it is created by a cross-functional and geographically diverse team. With every team member bringing their abilities and knowledge to the table, the strategy over time can only move from strength to strength. However, if not supported correctly, a cross-functional team working on strategy can be dysfunctional and chaotic, and result in a laborious and time-consuming approach to strategy development. Digital strategy platforms such as Nmblr offer an inclusive and structured process to facilitate a strategy discussion and allow people to bring forward ideas. They do this by: working against silos – the structure provided, levels the playing field. The guidance provided equips people from different disciplines to contribute to the conversation.

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Modern Phenotypic Drug Discovery

Article | June 30, 2022

Nature Reviews Drug Discovery makes these points well. It goes over historical and recent successes of the phenotypic approach, and discusses some areas that it's opening up for discussion and research. One of these is the long-vexed question of polypharmacology: what do you do when your active compound doesn't seem to have a single target, but rather hits a whole list of stuff at varying degrees of potency? Seen from a pure target-based viewpoint, this is a failure, and you'd better start working on something else. But to be honest, there are a lot of drugs out there (and not all of them ancient legacy compounds by any means) that work this way, even if their developers didn't think so at the time. So it's not to be disparaged on principle, but that said, it's still a difficult area to make progress in because of all the variables. A good enough phenotypic hit, though, makes its own case that it's worthy of further investigation and development, even if it's not "clean" by rigorous target-based standards. But as always, your phenotypic screen had better be a good one. That is, it had really better model the human disease in a useful way, and have a good signal/noise. The authors note that you're much better off with assays that involve a gain-of-function/gain-of-signal readout, as opposed to ones that could read out just through cellular stress or cytotoxicity, which is an invitation to chase your tail. Another area the paper brings up is searching lower-molecular-weight compounds than are usually screened, down to fragment-sized. There are quite a few useful drugs out there with really low molecular weights - ibuprofen, aspirin, metformin, dimethyl fumarate, lacosamide and more - and any screening program would be happy to have discovered something as useful as those. As the authors note, hits like these in phenotypic screens might be another case of polypharmacology, or they might be hitting pathways whose "tone" we have not understood well (and for which micromolar inhibitors might work out just fine). At any rate, there might be an opportunity for fragment phenotypic screening, and even of covalent fragments (which will call for even more attention to the validity of the underlying screening model, I'd say). The paper discusses the question of target ID, which for most phenotypic programs feels like a natural progression. Most of us are innately biased towards thinking in terms of drug targets, so when a phenotypic compound emerges we want to know what it's "really" doing. And most of the time, there is such a target in there somewhere, although finding it can be quite a haul. I know of several compounds that have been kicking around for years that are obviously doing something in the assays, but no one has ever been able to pin down quite what that is! This paper makes the case for getting out of a binary mindset for target identification. They point out, correctly, that target ID is a means to an end, and that you do not actually need to identify your target to go on to clinical trials and go to the FDA for approval. I always find it surprising to find how many people are surprised by that, but it's true. You also need to realize that knowing a target may not tell you nearly as much as you would want about a compound's mechanism of action, if your new target lands in the middle of a bunch of not-well-worked-out biology. There's a good case to be made that modern chemical biology and imaging techniques have made it easier to progress things, even if you're not quite sure how they're working. We can extract huge amounts of information about the cellular effects of a given compound, and if you do a good job of matching this against a closely related structure that's phenotypically inactive, you can make a lot of headway. This doesn't mean that you shouldn't bother trying to find the target - as mentioned, this is a great way to expand the knowledge of the underlying disease, and can lead to other new programs spinning off of the phenotypic effort. But it does mean that you shouldn't freeze in fear if you don't have a target to point to. The FDA wants to see safety and efficacy, and that's what we should want to see, too, for starters. But as the paper notes at the end, phenotypic screening is going to advance at the pace of good model development. Many of these same chem-bio tools can be brought to bear on this question as well, along with advances in cell culture, organoids, and other new assay technologies. You're not going to be able (realistically) to recapitulate all the features of a human disease, so you will probably find yourself concentrating on certain features that you can make the case for driving a project on. I was very happy to see this paper reference Jack Scannell's paper on translatability (blogged about here), because its point is crucial to the whole phenotypic screening endeavour. If your underlying assay is flawed, there is nothing you can do in any other part of the project to make up for it. A poorly translatable assay is a sign that you should spend your time trying to fix it, or to go do something entirely different instead. It is not a sign that you should just keep on going, because "it's the best thing we've got". If it isn't good enough, it isn't good enough. I don't get to quote A. E. Houseman much around here, but he's right: "The toil of all that be. Helps not the primal fault; It rains into the sea. And still the sea is salt." If you don't fix your assay up front, you are raining into the sea.

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Tips for Managing Chronic Pain Beyond Prescription Painkillers

Article | June 2, 2022

Painkillers like Oxycontin, Percocet, and Vicodin, have been prescribed by primary physicians, surgeons, dentists, and other healthcare providers to patients suffering from varying levels of pain. Though these medications have proven to be an effective source of pain relief, they have also proven to be highly addictive. In fact, it has even been reported that there are more cases of a drug overdose and deaths from prescription painkillers than heroin or cocaine. While there are a number of factors that play into this opioid epidemic, educating doctors and patients on alternative solutions to managing chronic pain is a great place to start combatting this nationwide crisis.

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What are the advantages of PCD Pharma Company?

Article | February 17, 2020

PCD Pharma stands for propaganda distribution. A PCD company gives brand name and support to its franchises. They also provide distribution rights and monopoly rights within a particular region. If a person wants to establish their business, it is a must for them to know the pros and cons of the business to make a sound decision. Needless to mention that PCD company has a lot to contribute in the medical filed. Worldwide in a medical field, A PCD Pharma Company is playing an essential and crucial role in the rapid growth. The pharma industry is progressing t a fast pace. The company uses the latest technologies for each brand which ensures the safety of products and accepts the responsibility of human health & life by providing better outcomes. To have a drug license number and company registration, the cost to establish the company is quite cost-effective that is15000-20000rs. So this gives people a brilliant opportunity to have their unit without digging a big hole in their bank balance. Indian produces exquisite quality products, which make pharma companies a considerable success.

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Fusion Pharmaceuticals Announces Presentation of Preclinical Data Supporting its FPI-1966 and FPI-2059 Targeted Alpha Therapies

Fusion | October 23, 2021

Fusion Pharmaceuticals a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, today announced the presentation of preclinical data that provide further support of its FPI-1966 and FPI-2059 targeted alpha therapies at the 34th Annual European Association of Nuclear Medicine Congress. These data reinforce the clinical dosing regimen of FPI-1966 and highlight the potential of FPI-2059 as an actinium-225 labelled precision medicine targeting NTSR1. "These data demonstrate the broad potential of our TAT platform across multiple validated targets overexpressed in a variety of solid tumors, We are pleased to share preclinical efficacy and tumor uptake data resulting from the administration of FPI-1966, and we believe strongly that this data will translate into meaningful results for patients with solid tumors overexpressing FGFR3 – a population with high unmet medical need. We look forward to initiating the Phase 1 study around the end of this year." Chief Executive Officer John Valliant, Ph.D Data from preclinical studies of FPI-1966, a TAT designed to target and deliver actinium-225 to cancer cells expressing FGFR3, were presented in an oral presentation titled, "FGFR3 Targeted Alpha Therapeutic [225Ac]-FPI-1966 induces regression in preclinical bladder xenograft model". Outcomes demonstrated that FPI-1966 when administered with vofatamab results in high tumor delivery and low off-target uptake. Further, the data showed therapeutic efficacy of FPI-1966 at both single and multiple doses in a preclinical bladder cancer xenograft model. Data from preclinical studies of FPI-2059, a TAT designed to target and deliver actinium-225 to cancer cells expressing neurotensin receptor 1 (NTSR1), were presented in an oral presentation titled "NTSR1 Targeted Alpha Therapeutic [225Ac]-FPI-2059 induces regression in preclinical colorectal xenograft model". The study results include a head-to-head comparison of therapeutic efficacy obtained from FPI-2059, which delivers an alpha emitting isotope, with [177Lu]-IPN-1087, which delivers a beta emitting isotope on the same targeting molecule. Results demonstrate superior efficacy with [225Ac]-FPI-2059 in a mouse xenograft model of colorectal cancer. Dr. Valliant continued, "Our science is based on the belief that alpha-emitting isotopes can provide significant therapeutic advantages compared to other commonly used radioisotopes. Preclinical results from our FPI-2059 product candidate provide further validation of this belief and support the diversification of our product portfolio to comprise multiple targeting vehicle types, including small molecules. We are pleased to be advancing further preclinical studies of FPI-2059 as we approach an investigational new drug (IND) filing in the first half of 2022." About FPI-1966 [225Ac]-FPI-1966 is a targeted alpha therapy designed to target and deliver an alpha emitting medical isotope, actinium-225, to cancer cells expressing FGFR3; a receptor that is overexpressed on several tumor types, including head and neck and bladder cancers. FPI-1966 utilizes Fusion's Fast-Clear™ linker to connect vofatamab, the human monoclonal antibody that targets FGFR3, with actinium-225. Vofatamab was previously evaluated as a therapeutic agent in a Phase 1b/2 trial and was reportedly well-tolerated. FPI-1966 is advancing to a Phase 1 study following the recent investigational new drug (IND) clearance About FPI-2059 FPI-2059 is a targeted alpha therapy combining actinium-225 with IPN-1087, for development as a targeted alpha therapy for various solid tumors. The molecule targets NTSR1, a promising target for cancer treatment, that is overexpressed in multiple solid tumors. IPN-1087 was in Phase 1 clinical development as a lutetium-177-based radiopharmaceutical for pancreatic ductal adenocarcinoma, colorectal cancer and gastric cancers expressing NTSR1. Fusion expects to submit an IND for FPI-2059 in the first half of 2022. About Fusion Fusion Pharmaceuticals is a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines. Employing a proprietary Fast-Clear™ linker technology, Fusion connects alpha particle emitting isotopes to various targeting molecules in order to selectively deliver the alpha emitting payloads to tumors. Fusion's lead program, FPI-1434 targeting insulin-like growth factor 1 receptor, is currently in a Phase 1 clinical trial. The pipeline includes FPI-1966, targeting the fibroblast growth factor receptor 3 (FGFR3), advancing to a Phase 1 study following the recent investigational new drug (IND) clearance; and FPI-2059, a small molecule targeting neurotensin receptor 1 (NTSR1). In addition to a robust proprietary pipeline, Fusion has a collaboration with AstraZeneca to jointly develop novel targeted alpha therapies (TATs) and combination programs between Fusion's TATs and AstraZeneca's DNA Damage Repair Inhibitors (DDRis) and immuno-oncology agents. Fusion has also entered into a collaboration with Merck to evaluate FPI-1434 in combination with Merck's KEYTRUDA® (pembrolizumab) in patients with solid tumors expressing IGF-1R. Fusion and Hamilton, Ontario-based McMaster University are building a current Good Manufacturing Practice (GMP) compliant radiopharmaceutical manufacturing facility designed to support manufacturing of the Company's growing pipeline of TATs. Forward Looking Statements This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding Fusion Pharmaceuticals Inc.'s (the "Company") future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the uncertainties inherent in the drug development process, including FPI-1966 and FPI-2059 early stage of development; the ability to move in-licensed targets forward in the clinic; the process of designing and conducting preclinical and clinical trials; the regulatory approval processes; the timing of regulatory filings; and the challenges associated with manufacturing drug products generally and radiopharmaceuticals specifically. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's quarterly report on Form 10-Q for the quarter ended June 30, 2021 as filed with the SEC and in any subsequent periodic or current report that the Company files with the SEC. All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Fusion may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

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Invitae to Acquire Ciitizen to Strengthen its Patient-Consented Health Data Platform to Improve Personal Outcomes and Global Research

Invitae | September 07, 2021

Invitae , a leading medical genetics company, today announced it has entered into a definitive agreement to acquire Ciitizen, a patient-centric consumer health tech company. Backed by a16z, Section 32 and Verily, Ciitizen is working to build a global platform to help patients collect, organize, store and share their medical records digitally. The acquisition would enhance Invitae's platform by providing patients an easy-to-use, centralized hub for their genomic and clinical information, which together comprise a powerful dataset with the potential to drive research and improve healthcare decision making. "Invitae is relentlessly pursuing a day when genetics is used routinely to improve healthcare for billions of people around the globe. We believe combining Ciitizen's state-of-the-art, transparent and patient-consented platform with our technologies and services will accelerate our evolution into a genome information company that informs healthcare throughout one's life. This would give us the ability to engage patients, create an innovative patient-centered data ecosystem and deliver better outcomes for everyone. Invitae views the acquisition of Ciitizen as an important part of its strategy to be the industry leader across the genetic testing, software and health information technology spaces," said Sean George, Ph.D., co-founder and CEO of Invitae. "Ciitizen has already helped patients take ownership of their medical records to optimize therapy for themselves and contribute their data towards a variety of goals, including research on rare diseases," said Anil Sethi, CEO and founder of Ciitizen. "Patients leave a breadcrumb trail of records behind them, and we believe access to this real-world data is key to personalized therapeutics in the future. The combination of lifelong health history together with Invitae's world-class genetic and data services would enable a digital ecosystem of personalized services for each patient. Democratization of patient-consented data is expected to improve outcomes by providing access to third-parties for whom the patient has granted consent. Unlike many health data companies, we operate on the premise that it's the patient's data, not ours." Invitae is working to aggregate results from the world's genetic tests into a single, easy-to-use service that makes genetic information accessible to all who can benefit from it - always with patient consent. Over the past five years, Invitae has completed 13 acquisitions that have expanded its testing menu, lowered the cost of its tests, improved its customer experience and enhanced its ability to attract partners. Invitae raised more than $1.4 billion since the beginning of 2021, in part to identify and acquire key assets that bring the company closer to delivering on its vision. The addition of Ciitizen is expected to empower Invitae to more quickly extend its platform, adding a complementary patient service that streamlines the process of collecting and organizing health information from any source and uses machine learning to transform the unstructured (and largely untapped) health information to enable better care decisions, find clinical trials, and power research using real-world evidence. In addition, as the use of Invitae testing and the Ciitizen service expands, third-party access to consented genomic and other clinical data can be democratized to power a variety of applications that can enhance Invitae's business and growth strategy. About Invitae Invitae Corporation is a leading medical genetics company, whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. About Ciitizen Ciitizen is a patient-centric consumer health technology platform that enables patients to collect, store and share their medical records in a single location. Ciitizen developed proprietary machine learning and AI technologies to abstract critical information from unstructured health records to advance the understanding of diseases, match patients with potentially life-saving clinical trials, and enable better care decisions. Ciitizen also provides valuable big data analytics and data quality technologies to the network of Health Information Exchanges (HIEs) to produce research-ready, regulatory-grade data within minutes, instead of hours or days, and ensure HIEs can comply with the Information Blocking regulations.

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Innovent and GenFleet Announce Exclusive Global License Agreement for GFH925 (KRAS G12C Inhibitor)

Innovent Biologics | September 02, 2021

Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, and GenFleet Therapeutics (Shanghai) Inc., a clinical-stage biotechnology company developing cutting-edge therapies in oncology and immunology, today jointly announced that they have entered into an exclusive license agreement for the development and commercialization of GenFleet's lead KRAS G12C candidate, GFH925 in China, including mainland China, Hong Kong, Macau and Taiwan with additional option-in rights for global development and commercialization. GFH925, GenFleet's lead KRAS G12C candidate, has recently received Investigational New Drug (IND) approval from National Medical Products Administration (NMPA) in China. Preclinical data showed that GFH925 has potential best-in-class activity that can effectively inhibit the growth of a variety of tumor cell lines carrying the KRAS G12C mutation, which may be helpful in accelerating the clinical validation of GFH925. In addition, other preclinical data have also demonstrated the potent potential for GFH925 in combination therapies. According to the agreement, Innovent will be responsible for clinical development and commercialization of GFH925 in China, while retaining option-in right for development and commercialization outside of China as well. Following approval of a New Drug Application (NDA), Innovent will leverage its broad commercialization capability that includes an experienced commercialization team with extensive nationwide coverage to roll out GFH925, with the goal to benefit cancer patients in China. GenFleet will continue to be responsible for supplying GFH925 for both development and commercial purposes in China. GenFleet will receive an upfront payment of US$22 million at signing. If Innovent exercises the option-in rights, GenFleet will receive up to US$50 million of global development support from Innovent. Upon achieving certain pre-specified milestones in development, registration, and annual sales performance of GFH925 globally, GenFleet is eligible to receive up to US$240 million in milestone payments in addition to tiered royalties based on annual net sales of GFH925 both in China and global markets. About GFH925 (KRAS G12C Inhibitor) Being developed by GenFleet Therapeutics, GFH925 is a novel, orally active, potent KRAS G12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRAS G12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of GFH925 towards G12C. Subsequently, GFH925 effectively inhibits the downstream signal pathway to induce tumor cells' apoptosis and cell cycle arrest. About Innovent Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK. Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 26 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 5 products. About GenFleet Therapeutics Dedicated to serving significant unmet medical needs, GenFleet Therapeutics established its proprietary R&D platform based on the deep understanding of disease biology, translational medicine, as well as researches into latest biological mechanism of cancer pathways, tumor microenvironment and human immunoregulation. GenFleet's rich and diversified pipeline highlights multiple cutting-edge products with novel mechanisms and global IP. Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates - both small molecules and biologics. Its pipeline includes over 13 programs in development, four of which have entered clinical stages. GenFleet is expected progress additional programs into clinics, as well as transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years.

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Fusion Pharmaceuticals Announces Presentation of Preclinical Data Supporting its FPI-1966 and FPI-2059 Targeted Alpha Therapies

Fusion | October 23, 2021

Fusion Pharmaceuticals a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, today announced the presentation of preclinical data that provide further support of its FPI-1966 and FPI-2059 targeted alpha therapies at the 34th Annual European Association of Nuclear Medicine Congress. These data reinforce the clinical dosing regimen of FPI-1966 and highlight the potential of FPI-2059 as an actinium-225 labelled precision medicine targeting NTSR1. "These data demonstrate the broad potential of our TAT platform across multiple validated targets overexpressed in a variety of solid tumors, We are pleased to share preclinical efficacy and tumor uptake data resulting from the administration of FPI-1966, and we believe strongly that this data will translate into meaningful results for patients with solid tumors overexpressing FGFR3 – a population with high unmet medical need. We look forward to initiating the Phase 1 study around the end of this year." Chief Executive Officer John Valliant, Ph.D Data from preclinical studies of FPI-1966, a TAT designed to target and deliver actinium-225 to cancer cells expressing FGFR3, were presented in an oral presentation titled, "FGFR3 Targeted Alpha Therapeutic [225Ac]-FPI-1966 induces regression in preclinical bladder xenograft model". Outcomes demonstrated that FPI-1966 when administered with vofatamab results in high tumor delivery and low off-target uptake. Further, the data showed therapeutic efficacy of FPI-1966 at both single and multiple doses in a preclinical bladder cancer xenograft model. Data from preclinical studies of FPI-2059, a TAT designed to target and deliver actinium-225 to cancer cells expressing neurotensin receptor 1 (NTSR1), were presented in an oral presentation titled "NTSR1 Targeted Alpha Therapeutic [225Ac]-FPI-2059 induces regression in preclinical colorectal xenograft model". The study results include a head-to-head comparison of therapeutic efficacy obtained from FPI-2059, which delivers an alpha emitting isotope, with [177Lu]-IPN-1087, which delivers a beta emitting isotope on the same targeting molecule. Results demonstrate superior efficacy with [225Ac]-FPI-2059 in a mouse xenograft model of colorectal cancer. Dr. Valliant continued, "Our science is based on the belief that alpha-emitting isotopes can provide significant therapeutic advantages compared to other commonly used radioisotopes. Preclinical results from our FPI-2059 product candidate provide further validation of this belief and support the diversification of our product portfolio to comprise multiple targeting vehicle types, including small molecules. We are pleased to be advancing further preclinical studies of FPI-2059 as we approach an investigational new drug (IND) filing in the first half of 2022." About FPI-1966 [225Ac]-FPI-1966 is a targeted alpha therapy designed to target and deliver an alpha emitting medical isotope, actinium-225, to cancer cells expressing FGFR3; a receptor that is overexpressed on several tumor types, including head and neck and bladder cancers. FPI-1966 utilizes Fusion's Fast-Clear™ linker to connect vofatamab, the human monoclonal antibody that targets FGFR3, with actinium-225. Vofatamab was previously evaluated as a therapeutic agent in a Phase 1b/2 trial and was reportedly well-tolerated. FPI-1966 is advancing to a Phase 1 study following the recent investigational new drug (IND) clearance About FPI-2059 FPI-2059 is a targeted alpha therapy combining actinium-225 with IPN-1087, for development as a targeted alpha therapy for various solid tumors. The molecule targets NTSR1, a promising target for cancer treatment, that is overexpressed in multiple solid tumors. IPN-1087 was in Phase 1 clinical development as a lutetium-177-based radiopharmaceutical for pancreatic ductal adenocarcinoma, colorectal cancer and gastric cancers expressing NTSR1. Fusion expects to submit an IND for FPI-2059 in the first half of 2022. About Fusion Fusion Pharmaceuticals is a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines. Employing a proprietary Fast-Clear™ linker technology, Fusion connects alpha particle emitting isotopes to various targeting molecules in order to selectively deliver the alpha emitting payloads to tumors. Fusion's lead program, FPI-1434 targeting insulin-like growth factor 1 receptor, is currently in a Phase 1 clinical trial. The pipeline includes FPI-1966, targeting the fibroblast growth factor receptor 3 (FGFR3), advancing to a Phase 1 study following the recent investigational new drug (IND) clearance; and FPI-2059, a small molecule targeting neurotensin receptor 1 (NTSR1). In addition to a robust proprietary pipeline, Fusion has a collaboration with AstraZeneca to jointly develop novel targeted alpha therapies (TATs) and combination programs between Fusion's TATs and AstraZeneca's DNA Damage Repair Inhibitors (DDRis) and immuno-oncology agents. Fusion has also entered into a collaboration with Merck to evaluate FPI-1434 in combination with Merck's KEYTRUDA® (pembrolizumab) in patients with solid tumors expressing IGF-1R. Fusion and Hamilton, Ontario-based McMaster University are building a current Good Manufacturing Practice (GMP) compliant radiopharmaceutical manufacturing facility designed to support manufacturing of the Company's growing pipeline of TATs. Forward Looking Statements This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995, including but not limited to the statements regarding Fusion Pharmaceuticals Inc.'s (the "Company") future business and financial performance. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are expressed or implied statements with respect to the uncertainties inherent in the drug development process, including FPI-1966 and FPI-2059 early stage of development; the ability to move in-licensed targets forward in the clinic; the process of designing and conducting preclinical and clinical trials; the regulatory approval processes; the timing of regulatory filings; and the challenges associated with manufacturing drug products generally and radiopharmaceuticals specifically. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's quarterly report on Form 10-Q for the quarter ended June 30, 2021 as filed with the SEC and in any subsequent periodic or current report that the Company files with the SEC. All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Fusion may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

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PHARMA TECH

Invitae to Acquire Ciitizen to Strengthen its Patient-Consented Health Data Platform to Improve Personal Outcomes and Global Research

Invitae | September 07, 2021

Invitae , a leading medical genetics company, today announced it has entered into a definitive agreement to acquire Ciitizen, a patient-centric consumer health tech company. Backed by a16z, Section 32 and Verily, Ciitizen is working to build a global platform to help patients collect, organize, store and share their medical records digitally. The acquisition would enhance Invitae's platform by providing patients an easy-to-use, centralized hub for their genomic and clinical information, which together comprise a powerful dataset with the potential to drive research and improve healthcare decision making. "Invitae is relentlessly pursuing a day when genetics is used routinely to improve healthcare for billions of people around the globe. We believe combining Ciitizen's state-of-the-art, transparent and patient-consented platform with our technologies and services will accelerate our evolution into a genome information company that informs healthcare throughout one's life. This would give us the ability to engage patients, create an innovative patient-centered data ecosystem and deliver better outcomes for everyone. Invitae views the acquisition of Ciitizen as an important part of its strategy to be the industry leader across the genetic testing, software and health information technology spaces," said Sean George, Ph.D., co-founder and CEO of Invitae. "Ciitizen has already helped patients take ownership of their medical records to optimize therapy for themselves and contribute their data towards a variety of goals, including research on rare diseases," said Anil Sethi, CEO and founder of Ciitizen. "Patients leave a breadcrumb trail of records behind them, and we believe access to this real-world data is key to personalized therapeutics in the future. The combination of lifelong health history together with Invitae's world-class genetic and data services would enable a digital ecosystem of personalized services for each patient. Democratization of patient-consented data is expected to improve outcomes by providing access to third-parties for whom the patient has granted consent. Unlike many health data companies, we operate on the premise that it's the patient's data, not ours." Invitae is working to aggregate results from the world's genetic tests into a single, easy-to-use service that makes genetic information accessible to all who can benefit from it - always with patient consent. Over the past five years, Invitae has completed 13 acquisitions that have expanded its testing menu, lowered the cost of its tests, improved its customer experience and enhanced its ability to attract partners. Invitae raised more than $1.4 billion since the beginning of 2021, in part to identify and acquire key assets that bring the company closer to delivering on its vision. The addition of Ciitizen is expected to empower Invitae to more quickly extend its platform, adding a complementary patient service that streamlines the process of collecting and organizing health information from any source and uses machine learning to transform the unstructured (and largely untapped) health information to enable better care decisions, find clinical trials, and power research using real-world evidence. In addition, as the use of Invitae testing and the Ciitizen service expands, third-party access to consented genomic and other clinical data can be democratized to power a variety of applications that can enhance Invitae's business and growth strategy. About Invitae Invitae Corporation is a leading medical genetics company, whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. About Ciitizen Ciitizen is a patient-centric consumer health technology platform that enables patients to collect, store and share their medical records in a single location. Ciitizen developed proprietary machine learning and AI technologies to abstract critical information from unstructured health records to advance the understanding of diseases, match patients with potentially life-saving clinical trials, and enable better care decisions. Ciitizen also provides valuable big data analytics and data quality technologies to the network of Health Information Exchanges (HIEs) to produce research-ready, regulatory-grade data within minutes, instead of hours or days, and ensure HIEs can comply with the Information Blocking regulations.

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BUSINESS INSIGHTS

Innovent and GenFleet Announce Exclusive Global License Agreement for GFH925 (KRAS G12C Inhibitor)

Innovent Biologics | September 02, 2021

Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, and GenFleet Therapeutics (Shanghai) Inc., a clinical-stage biotechnology company developing cutting-edge therapies in oncology and immunology, today jointly announced that they have entered into an exclusive license agreement for the development and commercialization of GenFleet's lead KRAS G12C candidate, GFH925 in China, including mainland China, Hong Kong, Macau and Taiwan with additional option-in rights for global development and commercialization. GFH925, GenFleet's lead KRAS G12C candidate, has recently received Investigational New Drug (IND) approval from National Medical Products Administration (NMPA) in China. Preclinical data showed that GFH925 has potential best-in-class activity that can effectively inhibit the growth of a variety of tumor cell lines carrying the KRAS G12C mutation, which may be helpful in accelerating the clinical validation of GFH925. In addition, other preclinical data have also demonstrated the potent potential for GFH925 in combination therapies. According to the agreement, Innovent will be responsible for clinical development and commercialization of GFH925 in China, while retaining option-in right for development and commercialization outside of China as well. Following approval of a New Drug Application (NDA), Innovent will leverage its broad commercialization capability that includes an experienced commercialization team with extensive nationwide coverage to roll out GFH925, with the goal to benefit cancer patients in China. GenFleet will continue to be responsible for supplying GFH925 for both development and commercial purposes in China. GenFleet will receive an upfront payment of US$22 million at signing. If Innovent exercises the option-in rights, GenFleet will receive up to US$50 million of global development support from Innovent. Upon achieving certain pre-specified milestones in development, registration, and annual sales performance of GFH925 globally, GenFleet is eligible to receive up to US$240 million in milestone payments in addition to tiered royalties based on annual net sales of GFH925 both in China and global markets. About GFH925 (KRAS G12C Inhibitor) Being developed by GenFleet Therapeutics, GFH925 is a novel, orally active, potent KRAS G12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRAS G12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of GFH925 towards G12C. Subsequently, GFH925 effectively inhibits the downstream signal pathway to induce tumor cells' apoptosis and cell cycle arrest. About Innovent Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK. Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 26 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 5 products. About GenFleet Therapeutics Dedicated to serving significant unmet medical needs, GenFleet Therapeutics established its proprietary R&D platform based on the deep understanding of disease biology, translational medicine, as well as researches into latest biological mechanism of cancer pathways, tumor microenvironment and human immunoregulation. GenFleet's rich and diversified pipeline highlights multiple cutting-edge products with novel mechanisms and global IP. Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates - both small molecules and biologics. Its pipeline includes over 13 programs in development, four of which have entered clinical stages. GenFleet is expected progress additional programs into clinics, as well as transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years.

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