Roots Analysis

Roots Analysis

Followers 0
Following 0
Over the years, monetary assistance from angel investors, venture capitalists and funding schemes of various public and private organizations / funds, along with assistance from regulatory authorities, have allowed start-ups / small companies to further their R efforts related to the ADC therapeutics.In this chapter, we have reviewed the various capital investments that have been made into the ADC therapeutics market.It includes details of only those instances wherein investments were made into different companies / research institutes for the development of ADC molecules, offering insights on how the overall market has evolved in terms of investment activity.We have also highlighted the most active venture capital investors in this domain.During our research, we were able to identify around 90 funding instances between 2011 and 2019, amounting to a total of nearly USD 4.7 billion.In fact, in 2019, we identified 6 instances of funding till July 2019.According to our research, more than 80% of the total investment (in terms of the amount invested) was made in last five years alone; a total amount of nearly USD 3.9 billion has been invested since 2015.
2
The pharmaceutical sector is one of the few industries that has been relatively less impacted amidst the COVID-19 pandemic.As the disease spreads, the demand for accurate diagnostic measures, and effective preventive and treatment solutions for COVID-19, is growing at a rapid pace.At the time of writing this article, more than 70 vaccines and around 100 therapeutic interventions were under development for the prevention and treatment of the disease, respectively.Moreover, there are heavy restrictions on international boundaries, preventing sponsors from leveraging the assistance of contract service providers.In this section, we have attempted to assess the impact of the COVID-19 pandemic on the businesses of peptide API contract service providers.Based on our assessment of the impact of the COVID-19 pandemic, the peptide API CMO market across the world, is likely to witness / have witnessed the following developments:Complete / partial disruption of normal operations and manufacturing taking place at sub-optimal capacityDecline in short-term demand from existing pharmaceutical sponsors / innovator companiesImmediate decline in outsourcing, especially from offshore locationsLimitations on workforce available on premises, as a result of government-imposed social distancing regulationsHeavy restrictions on cross border movement of goods and other logistical challenges, leading to the disruption of established supply chainsIncreased regulatory scrutiny Based on the abovementioned insights, it is unlikely that contract manufacturers are currently operating at full capacity.
It is worth mentioning that traditionally, biopharmaceutical companies preferred to keep manufacturing operations of such products in-house, due to a number of concerns related to intellectual property and quality.StrengthsIn order to meet the growing requirements of their client and to improve their capabilities, several Chinese contract manufacturers have entered into partnerships with each other.Further, the impact of globalization has led to the establishment of world class educational institutes in China, which, in turn, has resulted in the production of a qualified workforce that is available at a low cost.Experts believe that as outsourcing activities continue to rise in the biopharmaceutical market, CMOs may soon be confronted with a capacity crunch.Communication errors due to the language difference are known to be responsible for significant delays and setbacks.It has been observed that such errors might lead to the problems in the quality of production.
Given the multifaceted advantages of large volume wearable injectors, the field has witnessed an increase in the number of players involved in the development of such devices.The domain features the presence of over 35 companies which are involved in the development of over 70 large volume wearable injectors for the delivery of insulin and non-insulin drugs.Majority of the developers (35%) of large volume wearable injectors and drug-device combinations involved in the delivery of non-insulin drugs are start-ups or small-sized (less than 50 employees), followed by 26% large (501-5000 employees) and 22% very large companies (above 5000 employees).Examples of very large companies include (in alphabetical order, established before 2000) 3M, Amgen, Becton Dickinson, Roche and West Pharmaceutical Services.Devices developed for administration of non-insulin drugs have high storage capacities and are designed for either bolus or extended dosing of highly viscous formulations.In fact, around 65% of such devices have capacity to hold 6-10 mL of drug / therapy formulation, while 23% have storage capacity of more than 10 mL.In addition, some devices, such as Enable Injection’s enFuse™ On-Body Infusor and Enable Smart enFuse™ can hold up to 50 mL drug solution.Further, more than 15 drug device combinations are marketed / being evaluated for delivery of non-insulin drugs.
Outsourcing provides a platform for establishing strategic collaborations, which eventually helps players to augment their expertise in this domain, through access to lucrative and innovative cost cutting peptide synthesis technologies offered by CMOs.Moreover, given the success of certain blockbuster peptide drugs that are near patent expiry, such as (in alphabetical order) Lupron Depot,  OZEMPIC and Victoza, a number of biosimilars are anticipated to enter the market in the near future.The global overall peptide contract manufacturing market is estimated to be worth USD 3.9 billion by 2025, and this value is projected to reach USD 6.5 billion by 2030, growing at a CAGR of 15.8%, during the period 2020-2030.The outsourced component of the peptide API manufacturing market is likely to be worth USD 3.2 billion by 2030, growing at a CAGR of 11.2%, during the aforementioned time period.Whereas, the outsourced component of the peptide FDF manufacturing market is likely to be worth USD 2.5 billion by 2030, growing at a CAGR of 10.5%, during the aforementioned time period.On the other hand, the market for CMOs manufacturing peptide APIs using non-chemical / recombinant methods is expected to witness significant growth in the coming years as well.
With the increase in popularity of self-injection devices, several industry stakeholders have attempted to innovate the devices by incorporating advanced features to improve patient compliance and ensure accurate dosing.The ongoing R activity in this domain has led to a significant increase in the number of patents filed / granted associated with novel large volume wearable self-injection devices.Over the past few years, there has been a steady increase in the number of patents associated with these devices.In fact, after 2017, the number of patents filed / granted has increased significantly each year, across the globe.Specifically in 2019, the highest number of patents were published worldwide.Notable examples of the proprietary technologies, used in large volume wearable injectors, include (in alphabetical order) ECell technology (SteadyMed Therapeutics), SmartGuard technology (Medtronic) and VapourSoft technology (Bespak).
Over the last few decades, there has been a lot of research on the make-or-buy decision, mostly focusing on how different companies tend to make the right decision in this regard.Presently, we are led to believe that a detailed review of existing approaches and decision-making frameworks may help establish a better understanding of this process.Example illustrating Scenario 1:  In December 2019, Asymchem and Taizhou EOC Pharma entered into a manufacturing and supply agreement.Key highlights related to the agreement are as follows:The CDMO, Asymchem, agreed to offer drug development, production and regulatory support services to Taizhou EOC Pharma.As Asymchem’s manufacturing facility in located in China as well, it is likely to provide additional regional capacity to Taizhou EOC Pharma for its products.Further, Asymchem claims to have an experience of 25 years and the required technical expertise to cater to Taizhou EOC Pharma’s oncology-related drug development needs.In this scenario, it is safe to assume that the complexity of outsourcing is less, considering that Taizhou EOC Pharma, a Chinese company is engaging Asymchem, which is also based in the same region.In other word, the concerns associated with linguistic / sematic and logistics-associated barriers, are not applicable in this particular deal.Example illustrating Scenario 2:In January 2017, Enteris BioPharma entered into the manufacturing and supply agreement with KeyBioscience (a subsidiary of Nordic Bioscience).Key highlights related to the agreement are as follows:The CDMO, Enteris BioPharma agreed to assist in the GMP manufacturing of KeyBioscience’s metabolic peptides, by utilizing its proprietary technology Peptelligence.Further, the adoption of the innovative technology (Peptelligence) by KeyBiosciences is expected to add substantial value to its capabilities.Since Enteris BioPharma is located in the US, it presents an opportunity for KeyBiosciences to expand the geographical reach of its products.In this scenario, complexities are mainly subjected to logistic and language barriers since KeyBioscience is headquartered in Denmark, while Enteris BioPharma is based in the US.However, adoption of a novel production technology is anticipated to add high value to KeyBioscience in the long term, and could be a plausible reason to outsource the operations.Example illustrating Scenario 3:In August 2018, Dalton Pharma, a CDMO, entered into a manufacturing and supply agreement with Arch Biopartners.
The annual, global demand for therapeutic peptide APIs is estimated to be 2,145 kg in 2020, and this value is projected to reach about 3,800 kg by 2025, growing at a CAGR of 10%.Given that majority of the approved peptide drugs have lost patent exclusivity, the current demand is driven by both generics and new drugs, equally.It is worth highlighting that in 2017, there were 7 peptide drugs approved by the USFDA.The maximum share of the current manufacturing demand is captured by North America (48%), followed by Europe (30%), and is expected to increase in the near future.The global, annual capacity for small molecule APIs is primarily driven by the large and mid-sized companies.Although, there is a relatively higher number of mid-sized players in the peptide API contract manufacturing market, the global production capacity is undisputedly being driven by large and very large players.We have further analyzed the installed global capacity based on the scale of operation (preclinical / clinical and commercial) of the manufacturer.Example of companies that offer peptide API production services at all scales of operation are (in alphabetical order) AmbioPharm, CordenPharma, CPC Scientific and PolyPeptide.Majority (40%) of the peptide API contract manufacturing capacity is installed in North America.This is closely followed by Asia Pacific, which captures 34% of the overall, installed capacity for manufacturing of peptide APIs.
An informed capability assessment of different geographies, such as North America, Europe and Asia Pacific, is based on a variety of relevant parameters, such as number of CMOs, number of clinical sites, number of completed / active / planned clinical trials, number of patients enrolled, number of manufacturing facilities, number of CMOs offering manufacturing for API / FDF, number of CMOs having capabilities for clinical / commercial manufacturing, current demand for peptide therapeutics and installed manufacturing capacity in a particular region.Where, North America emerged as the most prominent region as per the above-mentioned parameters.It is worth highlighting that across all the regions, the peptide manufacturing facilities are capable of providing manufacturing services at the clinical scale.The figure presents the analytical distribution of the above-mentioned parameters in North America.
The number and geographical distribution of clinical trials are important indicators of both the therapeutic viability and future potential of innovative pharmacological interventions.These trials enable CDMOs / CMOs to estimate the clinical demand of peptide therapeutics across different geographies, therapeutic areas and trial phase.Moreover, the geographical distribution is a direct indicator of the various markets that are conducting trials or enrolling patients for clinical studies.Further, as more product candidates are approved by regulatory authorities across the globe, the number of clinical trials are also anticipated to increase.Whereas, in Asia Pacific and rest of the world, most of the active clinical trials are in phase III.This indicates that there is a higher clinical demand in North America and Europe, as compared to Asia Pacific, where a significant number of active trials are inching towards completion.
During our research, we came across several partnerships and collaborations that have been inked, during the period 2014-2019, between various stakeholders involved in the peptide therapeutics contract manufacturing domain.Additionally, a few licensing agreements were reported in given time period; examples include (in reverse chronological order) deals signed between Enteris BioPharma and Cara Therapeutics (August 2019), NUMAFERM and PEPDesign (July 2019) and Enteris BioPharma and Ferring Pharmaceuticals (February 2017).Whereas, most of the agreements were signed for clinical stage molecules (48%), followed by those inked for the production of peptide therapeutics at commercial (28%), and preclinical scales (24%).The maximum number of partnerships were signed by stakeholders based in the US.Moreover, we were able to identify various other development initiatives, such as opening of new facilities, and expansion of manufacturing facilities and capacity focused on peptides, which have recently been undertaken by companies in this domain, during the period of 2014-2019.Furthermore, the domain features the presence of recent peptide synthesis technologies that have made an impact on the peptide manufacturing process, such as chemo-enzymatic peptide synthesis technology, continuous flow technology and green chemistry.
Several industry players have established peptide manufacturing facilities across the world.During our research, we came across North America and Europe emerged as the current manufacturing hub for peptides, as 75% of the total facilities are presently located in these regions.Various companies were found to be involved in the manufacturing of peptide APIs, while few were focused on the manufacturing of peptide FDF.Our analysis also revealed that, some of the companies were involved in the manufacturing of both peptide API and FDF in the same facility.The key observations on the location of the manufacturing facility have been highlighted below:In North America, the US has emerged as the key hub for peptide manufacturing.Examples of players that have manufacturing facilities in the US include (in alphabetical order) Karebay Biochem, Peptide Institute, PolyPeptide and Sekisui Xenotech.Within Europe, the UK (22%) and Switzerland (17%) emerged as the key peptide manufacturing hubs.
Over the years, the peptide therapeutics domain has evolved significantly.However, the upsurge in demand for such treatment modalities has compelled developers to outsource some key operations, specifically the complex manufacturing process, to contract service providers, which enable reduction in cost as well as overall time to market.Further, companies offering only peptide FDF manufacturing services are (in alphabetical order) Ajinomoto Bio-Pharma, Baccinex, ChemPartner and UPM Pharmaceuticals.Further, the peptide contract manufacturing market is presently dominated by the presence of mid-sized companies (between 51 to 500 employees) and small companies (less than 51 employees), which collectively capture more than 70% of the dataset.Examples of companies that have more than 1,000 employees include (in alphabetical order) Asymchem, CordenPharma, Neuland and STA Pharmaceutical.This indicates that stakeholders are actively striving to adopt the one stop shop model and provide end to end services to customers worldwide.
Presently, peptide-based therapeutics represent a prominent class of therapeutic interventions.Currently, many peptide therapeutics are being developed for the treatment of oncological disorders.In fact, in 2018, about 75% of such therapeutic products were estimated to be available for the treatment of different cancer indications, accounting for global sales of more than USD 1 billion.Such therapeutics, when compared to recombinant antibodies and protein-based interventions, have been shown to demonstrate better tissue / cell penetration, owing to their small size and low immunogenicity.No.TypeProcessesSpecifications1ChemicalLiquid phase synthesis§ Used for producing peptides with < 8 amino acids§ Easy and inexpensive scale-up§ Difficult purification§ Not highly automated§ Long production cycle§ Produces only one product§ Requires additional set-up for the protection of C-terminal of the first amino acid2ChemicalSolid phase synthesis§ Used for producing long peptides in small quantities§ Easy purification§ Expensive purification§ Highly automated§ Short production cycle§ Extra steps are required for linkage and cleavage3ChemicalHybrid phase synthesis§ Combination of solid and solution phase§ Initial condensation reaction between two or more suitable peptides takes place in the solid phase§ Synthesis of longer peptides (>50 amino acids)3ChemicalMicrowave assisted technology§ More effective for the synthesis of difficult-to synthesize peptides§ Better peptide yield and purity§ Better reproducibility§ Faster reaction times§ High chances of racemization and dehydration4ChemicalLigation technology§ More effective for the synthesis of long peptides§ Uses chemical and enzyme-mediated technologies§ High yield§ Better chemo selectivity5RecombinantRecombinant Technology§ Used for producing immunogenic or biologically active peptides§ Easy introduction of unnatural amino acids§ More complicated solubilitySource: Roots Analysis A contract manufacturer is a third-party organization that offers manufacturing related services on a contract basis to other firms.The in-house development of peptide API requires necessary expertise and capabilities, including design, construction and maintenance of a facility which demands significant capital investments.
Rising complexities related to handling and administration of novel / advanced therapeutic options, have caused many device developers to outsource certain aspects of their businesses to contract service providers.Moreover, development process of drug delivery devices, such as high-volume injectors, involves multiple components (including electronic and mechanical modules), which need to have an appropriate design / size and user interface quality.Currently, close to nearly 30 players across the globe claim to offer manufacturing services to the developers of wearable injectors.Majority of these (37%) are mid-sized companies (201-1,000 employees), followed by 25% large companies (1,001-10,000 employees) and 21% small-sized companies (less than 200 employees).Further, this domain features the presence of 4 very large firms; examples include (in alphabetical order, headquartered in US) Battelle and SMC.It is worth highlighting that, most of the players are headquartered in North America (50%) followed by Europe (42%).
Currently, three drug-device combinations, namely Herceptin® SC Injector (Roche),  Neulasta® (pegfilgrastim) OnPro™ Kit (Amgen / Insulet) and Repatha® Pushtronex™ System (Amgen / West Pharmaceutical Services) have received USFDA approval and  D-Mine® Pump (EVER Pharma / Sensile Medical) has received the CE approval.The market is poised to witness significant growth as several more large volume wearable injectors are approved for the delivery of non-insulin drugs, in the foreseen future.Our estimates suggest that the market for devices designed to deliver non-insulin drugs is expected to grow from to USD 600 million by 2030, at an annualized rate of close to 39%.The revenues in 2025, are expected to be dominated by patch pump injectors (65%) due to their convenient usage and ergonomic handling.This trend is likely to persist in the future as well.Further, revenues from the sales of disposable injectors are likely to represent the majority market share (85%) in 2030; this is primarily due to the fact that these devices are safer to use in comparison to reusable injection devices.
To meet the increasing demand for patient-friendly and safe options for drug administration, the drug developers are expected to broader their portfolio of drug candidates to make them favorable for delivery through self-injection systems.We identified several parameters which affect the likelihood of the drug to be delivered via the large volume wearable injectors.These include the drug’s volume and dosage, dose frequency, dose type, route of administration, target disease indication and year of patent expiry (in case of marketed drugs).In fact, in an interview with the chief executive officer of a US-based medical device company, he stated that “There is significant opportunity of these devices for the delivery of both biologics and small molecules.” Based on our proprietary scoring criteria, subcutaneously delivered drugs have the highest likelihood to be administered via the large volume injectors.Moreover, majority of the large volume wearable injectors have been designed with the needle / cannula systems which can penetrate the epidermis to deliver the drug to the subcutaneous capillary and lymphatic vessels where it is readily absorbed.
With the increase in popularity of self-injection devices, several industry stakeholders have attempted to innovate the devices by incorporating advanced features to improve patient compliance and ensure accurate dosing.The ongoing R activity in this domain has led to a significant increase in the number of patents filed / granted associated with novel large volume wearable self-injection devices.Over the past few years, there has been a steady increase in the number of patents associated with these devices.In fact, after 2017, the number of patents filed / granted has increased significantly each year, across the globe.Specifically in 2019, the highest number of patents were published worldwide.Notable examples of the proprietary technologies, used in large volume wearable injectors, include (in alphabetical order) ECell technology (SteadyMed Therapeutics), SmartGuard technology (Medtronic) and VapourSoft technology (Bespak).
Such deals are inked to not only allow companies to expand their respective product / service portfolios, but also gain additional capabilities in emerging technologies.In the domain of large volume wearable injectors, we identified unique types of partnership deals that were inked between different stakeholders.These include product / technology integration, product development / commercialization, distribution, licensing, merger / acquisition, manufacturing / supply, clinical trial, services agreement and others.During our research, we found that the number of partnerships has increased steadily between 2015 and 2020.It is important to highlight that the maximum number of deals (25) were signed in 2018.Majority of the deals (7) signed in 2018 were product development and commercialization agreements, followed by 6 distribution agreements.In the first quarter of 2020, 5 partnerships have been inked between various stakeholders.Product / technology integration agreements account for 29% of the total number of deals inked in the given period of time.
Given the multifaceted advantages of large volume wearable injectors, the field has witnessed an increase in the number of players involved in the development of such devices.The domain features the presence of over 35 companies which are involved in the development of over 70 large volume wearable injectors for the delivery of insulin and non-insulin drugs.Majority of the developers (35%) of large volume wearable injectors and drug-device combinations involved in the delivery of non-insulin drugs are start-ups or small-sized (less than 50 employees), followed by 26% large (501-5000 employees) and 22% very large companies (above 5000 employees).Examples of very large companies include (in alphabetical order, established before 2000) 3M, Amgen, Becton Dickinson, Roche and West Pharmaceutical Services.Devices developed for administration of non-insulin drugs have high storage capacities and are designed for either bolus or extended dosing of highly viscous formulations.In fact, around 65% of such devices have capacity to hold 6-10 mL of drug / therapy formulation, while 23% have storage capacity of more than 10 mL.In addition, some devices, such as Enable Injection’s enFuse™ On-Body Infusor and Enable Smart enFuse™ can hold up to 50 mL drug solution.Further, more than 15 drug device combinations are marketed / being evaluated for delivery of non-insulin drugs.
More

Top