Medtronic Launches RDN Therapy for Hypertension in China; Tasly's Controlling Stake May Change; ImmuneOnco Terminates $2B BD Deal

A Total of 3 Brief News Items | Estimated Reading Time: 3 Minutes◆◆ ◆

01

Medtronic's New Therapy Opens a "New Track" for Hypertension Treatment

Opening Up Industry Imagination: RDN Therapy Paves New Pathway for Hypertension Treatment

Cardio-cerebrovascular diseases are the leading "killer" causing disease-related deaths in China, with an annual death toll reaching several million. What is less known, however, is that more than half of these cases share a common cause – they are related to hypertension.

The Blue Paper on the Current Situation of Hypertension Prevention and Treatment in China 2018 shows that the number of adult patients in China is expected to reach 358 million, with approximately one in every four adults being a hypertension patient. Like Jaqen H'ghar, the Faceless Man from "Game of Thrones," hypertension often strikes "silently," causing immense damage.

At the end of April this year, a piece of news attracted widespread attention in the industry: Medtronic's Symplicity Spyral™ RDN system received NMPA approval for marketing in China. As the first product of its kind to be launched in China, it has pioneered a new track for renal artery sympathetic denervation (RDN) procedures in the country.

For hundreds of millions of patients in China, this approval is of great significance - it means that the third type of hypertension therapy has officially entered the country. With an interventional procedure, it can address challenges beyond drug treatment, thereby significantly reducing the difficulty of disease management.

To learn more about the therapy, MedTrend specially interviewed Tao Jia, Vice President of Medtronic's Coronary and Renal Denervation Business Operations in China. This is an important pipeline he manages, currently in the early stages of promotion, with clinical communications across China filling up his schedule. "Both the company and the clinics have high expectations." The product launch is just the beginning; at this stage, he feels both pressure and motivation. "The true significance of my work lies in ensuring that a large number of hypertension patients can benefit from this new therapy as soon as possible."

01

The "Third Horse" of Hypertension Treatment

As a chronic disease that requires lifelong management, the mainstream treatments for hypertension have previously been of two types: medication and lifestyle interventions, such as weight loss, exercise, and low-salt diets. However, anyone who has a person with hypertension nearby or is a patient themselves knows how difficult it is to change one's lifestyle habits, let alone adhere to them for a lifetime.

According to data from the Chinese Hypertension Prevention Guidelines, only about 16.9% of hypertensive patients can effectively control their condition, meaning that for every five hypertensive patients, more than four are at high risk of cardiovascular events.

There are two main reasons behind this.

First, there is poor compliance. Global relevant statistical data shows that 50% of patients擅自停药 within one year after starting medication, whether due to insufficient understanding, concerns about side effects, or inability to persist.

Second, there is a lack of treatment options. Even if patients can adhere to medication, there are still cases of drug-resistant hypertension where existing drug therapies "fail."

Renal Denervation (RDN) as a completely innovative method for lowering blood pressure provides a third treatment option for hypertension.

According to the description on the official website of the National Medical Products Administration, Medtronic's approved Symplicity Spyral™ RDN system lowers blood pressure by physically blocking the transmission of sympathetic nerve excitement. Compared with traditional drug treatments, it can effectively avoid the influence of factors such as patient compliance and drug half-life, providing a new auxiliary treatment method for patients with refractory hypertension.

This is also significant for Tao Jia himself, "One of my relatives has been a hypertension patient for over 20 years, continuously taking medication with fluctuating blood pressure control. Now, there is finally a new treatment option, and she is also considering trying it." According to him, RDN therapy represents a leap in hypertension treatment from the era of medication alone to minimally invasive surgical treatment, akin to paving a 'highway' for hypertension therapy.

02

"Resolute Practitioners": Walking a Lonely and Difficult Path

The pathogenesis of hypertension is complex, one of which is due to the overexcitation of the sympathetic nervous system, especially the renal artery sympathetic nerves. The increased activity of efferent and afferent nerves between these nerves and the brain can induce hypertension in multiple ways, such as increasing heart rate and enhancing vascular constriction.

As early as the 1840s, doctors attempted to use surgical methods to sever sympathetic nerves. After the evolution of technology, the latest research on RDN therapy began in the early 21st century. The principle, simply put, is to disconnect the connection with the brain, quieting down the overactive sympathetic nerves, thereby achieving the goal of controlling blood pressure.

An innovative medical technology cannot do without rigorous clinical testing. Medtronic has been on the path of accumulating evidence-based medical evidence for more than a decade.

Starting from 2009, Medtronic successively initiated the Symplicity HTN-1 and HTN-2 clinical trials, which preliminarily verified the efficacy and safety of RDN technology in controlling hypertension.

In 2014, based on clinical feedback from the first-generation product and the anatomical location of renal artery sympathetic nerve distribution, Medtronic launched the second-generation RDN system after validation through the HTN-3 clinical trial.

In 2017, to further verify feasibility, Medtronic launched the broader HTN Off-Med/On-Med project, conducting comparative trials on patients who were not taking antihypertensive drugs and those who were.

More than a decade of dedicated exploration has, in fact, been a profound challenge in understanding the potential of technology and the perseverance in execution. According to Tao Jia, the HTN-3 study in 2014 failed to meet expectations, which led to a loss of confidence in the industry and many companies abandoning RDN development. However, Medtronic chose to persevere. "We re-established our advisory board, inviting numerous clinical experts to refine improvements from every detail, ensuring each step was based on scientific evidence and real-world outcomes. Finally, in the subsequent HTN Off-Med/On-Med studies, the effectiveness of RDN was once again validated."

From another perspective, the reason why Medtronic has the confidence to persist is due to its years of technical accumulation in radiofrequency ablation. Whether it is electrode design or energy transmission, it has no lack of unique features. The second-generation RDN system is precisely the "culmination" of Medtronic's technological innovations.

On the one hand, it features a unique four-electrode spiral circumferential design, which is easy to operate and can achieve 360-degree "full-coverage" complete ablation.

Through the improvement of the radiofrequency catheter, the second-generation Symplicity Spyral™ catheter can ablate blood vessels with diameters ranging from 3-8mm. It also features a spiral circumferential design with four electrodes, allowing for complete ablation in all four quadrants of both the main renal artery and its branches. This enables surgeons to perform procedures more accurately, comprehensively, and conveniently.

On the other hand, an AI "alert line" has been set up to further reduce surgical risks, ensuring precise radiofrequency without damaging surrounding tissues.

Safety is "monitored" by artificial intelligence, and once there is a deviation from the preset ablation parameters, the machine will automatically shut off the ablation energy at the ablation site, reducing human error during the procedure. Precision comes from the system's low-power, controllable radiofrequency (RF) energy, which allows for exact control of intensity and delivery time, ensuring therapeutic effectiveness without damaging surrounding non-target organs and tissues.

With the support of innovative technologies and positive data, the Symplicity Spyral™ RDN system has demonstrated its significant role in treating resistant hypertension and drug-intolerant hypertension. It has been recommended by expert panels in multiple clinical studies, including the 2023 European Society of Hypertension Guidelines, and has been launched in 75 countries and regions worldwide, benefiting approximately 25,000 patients.

03

Seeking "Synchronization between China and the U.S." from Clinical Trials to Approval

About one in every four adults has hypertension, indicating a significant unmet need for hypertension treatment in China. Tao Jia noted that Medtronic has been actively promoting the adoption of this therapy in China.

Localized clinical trials are the first step to ensure approval.

Leveraging the policy advantages of the CIIE and Boao Pilot Zone, in April 2021, the Symplicity Spyral™ RDN System completed its first implantation in China and launched the GSR DEFINE CHINA real-world study in 2022, enrolling more than 50 Chinese patients with hypertension. The number of participants and the enrollment rate led among the global clinical trials for this therapy.

Moreover, thanks to the green channel for innovative medical devices and the openness of the National Medical Products Administration (NMPA) towards innovative technologies, the system was approved in China only about six months later than the U.S. FDA approval, which is quite rare across the entire innovative medical device industry. The Symplicity Spyral™ RDN System has thus become the world's first interventional treatment device system for hypertension to receive approvals in the United States, the European Union, and China.

However, the approval and market launch of innovative therapies is only "the first step of a long march," with countless "hurdles" yet to overcome. Tao Jia compared this process to a child's growth and has drawn up a series of "task lists" for it.

First, increase the promotion efforts. Enable more clinicians to understand the third type of hypertension therapy, and on the other hand, assist doctors in screening patients to identify the most suitable candidates for this treatment.

Secondly, participate in the establishment of a training system, standardized operating procedures, and a full-process management mechanism. Among these, the professional clinical simulation operation courses offered by the innovation centers of Medtronic in Shanghai and Chengdu can help carry out extensive professional clinical education for RDN therapy.

Third, assist doctors in postoperative management and follow-up. Hypertension is a long-term chronic disease management process, and after surgery, a progressive drug management and adjustment process must be carried out, including changes in lifestyle.

"Although the task is daunting, Tao Jia and his team are full of confidence. 'The new therapy is still in its infancy, so it's crucial to build a solid foundation. In the future, we hope to work with associations, clinical experts, and partners to standardize the promotion and implementation of the new therapy as much as possible.'"

The innovation of medical technology has no end, and the upgrading of clinical needs is an eternal call.

(Source: MedTrend)

02

Tasly's Controlling Stake May Change

On the first day of August, a重磅消息exploded in the medical industry's social circles. An announcement by Tasly Pharmaceutical Group Co., Ltd. (referred to as Tasly) truly surprised many industry professionals.

Tasly Issues Announcement Stating That It Has Received Notice from Its Controlling Shareholder, Tasly Biopharmaceuticals Industry Group (Abbreviated as: Tasly Industry Group), Regarding the Planning of a Share Transfer. This Matter May Lead to a Change in the Company's Control. Meanwhile, Trading Will Be Suspended Starting from August 1, 2024, with an Expected Suspension Period of No More Than Two Trading Days.

Upon the release of the news, many industry insiders expressed "shock" to E Pharmacy Manager, and the capital market was also rife with speculation.

After all, since its establishment in 1994, Tasly has become one of the leading enterprises in the traditional Chinese medicine (TCM) industry, relying on its core product, the Compound Danshen Dripping Pill. Its business model and innovative strategies have consistently been at the forefront of the industry. Moreover, Tasly's financial performance in 2023 has just achieved a significant turnaround, with net profits attributable to shareholders increasing from -RMB 275 million in 2022 to an impressive RMB 1.071 billion.

The sudden news of a change in control has inevitably sparked curiosity in the industry about what exactly happened behind the scenes?

Although Tasly's announcement did not disclose the other party involved in the transaction, it has already sparked heated discussions in the capital market. Currently, there are three main types of analysis in the capital market: one is state-owned capital, another is existing shareholders, and the third is companies that have relevant cooperation with Tasly in the digitalization of traditional Chinese medicine.

Among various perspectives, state-owned assets seem to have gained the upper hand.

From the perspective of the current stage of industrial development, "state-owned capital entering the market" does indeed align with the previous trend in the traditional Chinese medicine (TCM) industry. Ultimately, we will have to wait until Tasly resumes trading for the outcome to become clearer. However, state-owned capital taking the lead in the TCM industry is already an inevitable trend.

State-owned Assets Reassume Control of the "Big Picture" in the Traditional Chinese Medicine Industry

More and more signs show that state-owned capital is regaining control of the "overall situation" in the traditional Chinese medicine industry, and the proportion of traditional Chinese medicine enterprises with state-owned capital backgrounds in the entire industry is quietly rising.

According to statistics from E Pharmacy Manager, among the top ten Chinese medicine listed companies by market value, up to 70% of the enterprises have state-owned backgrounds. Notably, the top six Chinese medicine stocks by market value are all state-owned, including Pien Tze Huang, Yunnan Baiyao, China Resources Sanjiu, Tong Ren Tang, Baiyun Mountain, and Dong'e Ejiao. Among them, Pien Tze Huang, with a market value exceeding 100 billion yuan, has become the highest-valued Chinese medicine company with a state-owned background.

Among a group of listed traditional Chinese medicine companies, Tasly ranks tenth in market value. If industry predictions are correct and Tasly eventually comes under state-owned control, the number of state-owned traditional Chinese medicine stocks in the top ten by market value would increase to eight. Competition among state-owned enterprises in the traditional Chinese medicine industry will become even more intense.

In addition, Zhejiang Jolly Pharmaceutical, Conba Pharmaceutical, KPC Pharmaceuticals, Ma Yinglong Pharmaceutical, Taiji Group, Jiangzhong Pharmaceutical, Daren Tang, and Kangmei Pharmaceutical, all of which have state-owned capital backgrounds and market values exceeding 10 billion yuan.

Why Does State-Owned Capital Favor the Traditional Chinese Medicine Industry?

A source with work experience at a local State-owned Assets Supervision and Administration Commission once revealed to E Pharma Manager that, driven by the dual policies of "strengthening and expanding state-owned capital and enterprises" and "vigorously encouraging the development of traditional Chinese medicine," state-owned capital has shown strong interest in high-quality TCM assets.

According to the "2023 Pharmaceutical Industry Operation Report" released by the China Pharmaceutical Enterprise Management Association, apart from the outstanding performance of Chinese herbal pieces and proprietary Chinese medicines, which achieved positive growth in revenue and profit, most other pharmaceutical industry segments experienced negative growth and significant fluctuations. This indicates that the current high prosperity of traditional Chinese medicine is clearly more attractive to state-owned capital for high-quality investment targets.

Secondly, the products of many important enterprises involve state secrets, such as nationally protected varieties, confidential formulas, or rare raw material resources like musk, cow-bezoar, and bear bile. Additionally, some unique processing techniques for these materials are also highly favored by state-owned capital.

In the past period, China Resources Pharmaceutical Group and Sinopharm Group have shown clear signs of focusing on the traditional Chinese medicine (TCM) sector. After China Resources acquired Kunming Pharma in 2022, its TCM sector now includes four listed companies: Kunming Pharma Group, China Resources Sanjiu, China Resources Jiangzhong, and Dong'e Ejiao. Sinopharm Group’s TCM sector originally had two listed companies—Taiji Group and China Traditional Chinese Medicine. However, following the privatization of China Traditional Chinese Medicine in February this year, there has been speculation that China Traditional Chinese Medicine might be integrated with another TCM company under Sinopharm, Taiji Group. If this strategy is indeed implemented, Taiji Group will become the sole TCM listed company under Sinopharm Group.

Behind the "Cycle" of Industrial Attributes

Only by understanding history can we see the evolution of the current landscape. The development of the pharmaceuticals industry is undergoing a cycle.

Taking the development of the traditional Chinese medicine (TCM) industry as an example, before 1990, the TCM industry in China was almost entirely dominated by state-owned enterprises. Entering the 1990s, a group of private enterprises that would later become "famous in the industry" emerged like mushrooms after rain. Whether it is Buchang Pharmaceutical, established in 1993, Tasly Group, founded in 1994, Kangmei Pharmaceutical, established in 1997, or Yiling Pharmaceutical, founded in 2001... all these companies have now secured a place in the TCM industry.

Almost at the same time, a wave of state-owned enterprise reform swept across China. State-owned traditional Chinese medicine enterprises in various regions underwent restructuring one after another—some completed mixed reforms while maintaining state capital control, while others directly joined the ranks of private enterprises. Kangenbei, formerly known as Lanxi Yunshan Pharmaceutical Factory, transformed into a private enterprise during this period and successfully went public.

During that period of great prosperity in the market economy, the share of private capital in the market was no less than that of state-owned capital, and even slightly stronger. However, since entering the 21st century, a new round of changes has begun to emerge, with frequent typical cases in some industries.

Tracing back, in 2015, the entry of Guangxi state-owned assets into Zhongheng Group was a typical private enterprise relief action. At that time, Zhongheng Group was experiencing a broken capital chain of its actual controller, and the former actual controller and chairman, Xu Shuqing, was under investigation for suspected unit bribery and had been taken compulsory measures, which pushed the company into a difficult situation. In the end, Guangxi Investment Group, under the Guangxi state-owned assets, took over.

But the more intensive "change of hands" from private to state-owned enterprises in the Chinese medicine industry can be traced back to around 2020. This is inseparable from a major background. After the introduction of the "Three-Year Action Plan for State-Owned Enterprise Reform (2020-2022)," state capital accelerated the acquisition of traditional Chinese medicine assets.

Since then, the story of state-owned assets taking control of traditional Chinese medicine enterprises has been unfolding continuously, with well-known typical cases in the industry being abundant. Upon review, there are mainly two types of situations.

One type is that private enterprises introduce state-owned capital in an attempt to save their operational difficulties and declining performance.

In 2020, Conba announced the change of ownership to state-owned assets, with Zhejiang Provincial Traditional Chinese Medicine Health Industry Group, a wholly-owned subsidiary of Zhejiang International Trading Group, becoming its controlling shareholder. The reason behind this move was that Conba urgently needed to reverse the困境of facing multiple challenges in operations and a sharp decline in performance in 2019. The introduction of state-owned assets was an active choice made by Hu Jiqiang, the then chairman of Conba.

In the same year, Zuoli Pharmaceutical, which owns the exclusive blockbuster product Wuling Capsule, also introduced state-owned capital to "save the market." The medical health industry platform under the Zhejiang Provincial State-owned Assets Supervision and Administration Commission (Zhejiang Medical Health Group Co., Ltd.) took over, providing financial support and generating certain synergies. The underlying reason also pointed to "self-rescue," as Zuoli Pharmaceutical's performance had been deteriorating earlier, with the situation once becoming extremely severe and cash flow strained.

Once a千亿白马股,康美药业 faced a similar fate. In 2021, after being embroiled in the largest fraud case in the history of China's A-share market,康美药业 brought in state-owned广药集团 to "save" itself. In the same year, due to debt repayment difficulties,广誉远 was taken over by山西国资……

From the development in recent years after being taken over by state-owned enterprises, this group of traditional Chinese medicine companies that were once in trouble has temporarily stepped out of the mire. Conba returned to the growth track with a performance breakthrough; Zorya seized the opportunity and maintained high growth in performance; Kangmei Pharmaceutical also successfully removed the delisting risk warning and came back to life...

Another situation is that, due to their own development needs, the internal integration of the traditional Chinese medicine industry has intensified.

Over the past two years, several Chinese state-owned traditional Chinese medicine (TCM) enterprises have optimized their asset structures and improved corporate efficiency and value by completing equity transfer or acquisition transactions to adapt to market changes. During this period, Sinopharm Holding Taiji and CR Sanjiu became controlling shareholders of Kunming Pharmaceutical Corporation... All these are typical examples.

Apart from listed companies, many local state-owned enterprises in China have also frequently engaged in mergers and acquisitions of unlisted traditional Chinese medicine (TCM) companies, with numerous cases to that effect. For instance, in the second half of 2023, Ziguang Chenji, a century-old TCM company, underwent a change in equity, with its actual controller becoming the State-owned Assets Supervision and Administration Commission of Shanxi Province.

This round of state-owned assets taking control of the "overall situation" reflects a broader perspective: under the current circumstances, the entry of state-owned capital into private Chinese medicine companies is considered a two-way choice, with each party getting what it needs. From the perspective of private Chinese medicine enterprises, a series of past instabilities have generally subjected them to dual pressures in operation and financing. Selling part of their equity to reduce debt became a common choice at that time. On the other hand, by virtue of the inherent advantage of national credit, state-owned enterprises find it easier to secure loans and issue bonds at lower costs. Considering the long-term sustainable development of their enterprises, many private entrepreneurs are also willing to sell their shares to state-owned capital.

As for the ultimate development of the traditional Chinese medicine (TCM) industry, it remains worth watching. At the very least, after continuous integration and strengthening by leading players, the TCM industry will present a markedly different landscape in five to ten years. It even invites speculation that, before long, a "state-owned super pharmaceutical group" may take the lead in the TCM field.

(Source: E Pharm Manager)

03

Immunotech BD $2 Billion

On August 1, 2024, Immgene-B (01541) announced that it had entered into an exclusive out-licensing agreement with SynBioTx Inc., a wholly-owned subsidiary of Instil Bio, Inc (NASDAQ: TIL): Immgene will grant SynBioTx Inc. the development and commercialization rights outside of Greater China for its two innovative pipeline products under research, IMM2510 (VEGFxPD-L1 mAb-Trap) and IMM27M (CTLA-4, ADCC-enhanced), while retaining the rights for these two products within Greater China. Immgene will receive an upfront payment and near-term payment totaling 50 million US dollars, as well as subsequent development, registration, and commercialization milestone payments exceeding 2 billion US dollars, along with single-digit to low double-digit sales royalties outside of Greater China.

IMM2510, independently developed by ImClone (Shanghai) Limited, is a bispecific molecule targeting VEGF and PD-L1, adopting a monoclonal antibody-receptor recombinant protein (mAb-Trap) structure. IMM2510 can inhibit tumor angiogenesis by blocking the VEGF/VEGFR signaling pathway, thereby suppressing tumor growth and metastasis and making tumor cells more sensitive to immune responses. At the same time, it activates T cells, natural killer cells, and macrophages by blocking the PD-L1/PD-1 interaction and inducing Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activities, thereby exerting anti-tumor immune therapeutic effects.

Bispecific molecules targeting both PD-(L)1 and VEGF hold significant market potential for the treatment of malignant solid tumors. In May this year, Akeso Biopharma announced positive results from a Phase III clinical trial of Ivonescimab (a PD-1/VEGF bispecific antibody) as a monotherapy head-to-head against Keytruda (K药) in first-line treatment of PD-L1 positive NSCLC, fueling industry anticipation that it could replace PD-1 monoclonal antibodies like Keytruda in this indication. PM8002 (PD-L1/VEGF bispecific antibody) from Promab Biotechnologies also demonstrated impressive clinical data in triple-negative breast cancer. In 2022 and 2023, Akeso and Promab separately entered into substantial licensing partnerships with Summit Therapeutics and BioNTech, respectively.

As one of the VEGF/PD-L1 bispecific molecules in the first tier of clinical development progress in China, multiple projects of IMM2510 from ImmunoOnco have entered the clinical phase Ib/II stage, including monotherapy and combination therapy projects. The phase I dose escalation results published at the 2024 ASCO Annual Meeting showed that IMM2510 was generally well tolerated and demonstrated positive efficacy signals in solid tumors: at different doses, partial responses (PR) were achieved in two non-small cell squamous cell carcinoma patients who had previously failed immunotherapy and one thymic squamous cell carcinoma patient. Among seven solid tumor patients with stable disease (SD), four achieved SD with tumor shrinkage of more than 15% (two of whom had non-small cell lung cancer).

Another product in this transaction, IMM27M, is a next-generation CTLA-4 antibody with enhanced ADCC activity. It can induce a potent immune response targeting CTLA-4 overexpression and immunosuppressive regulatory T cells, promoting the clearance of regulatory T cells from the tumor microenvironment (TME), thereby enhancing the anti-tumor response of T cells.

IMM27M has completed patient recruitment for the Phase I dose escalation. Data presented at the 2023 ASCO Annual Meeting showed that IMM27M was generally well-tolerated: no dose-limiting toxicity (DLT) was observed in all subjects across a wide dose range. Positive efficacy was observed in two heavily pretreated patients with hormone receptor-positive (HR+) advanced breast cancer (both achieved PR); tumor shrinkage of over 20% (SD) was observed in one patient with advanced recurrent solid tumors. Breast cancer is the most common malignant tumor in women. According to WHO data, in 2022, 2.3 million women worldwide were diagnosed with breast cancer, and hormone receptor-positive breast cancer accounts for approximately 70% of all breast cancer cases.

The positive efficacy of IMM2510 and IMM27M in lung cancer, breast cancer, and other solid tumors has laid a strong foundation for the subsequent development of these two products in the highly promising solid tumor market. With the support of collaborators and the U.S. capital market, international clinical progress is expected to advance rapidly in the future.

01

Differentiated Advantages of CD47

Since its inception, ImmunoMab has been labeled as a biotech company focused on CD47 target research and development. Its core product, Tidapeximab (IMM01), has received approval for Phase III pivotal clinical trials in three indications. Among them, the Phase III pivotal clinical trial of IMM01 in combination with Tislelizumab for PD-(L)1 antibody-refractory classical Hodgkin's lymphoma (cHL) completed the first patient dosing in early July.

As a key macrophage checkpoint, CD47 is expressed on the surface of various tumor cells and was once considered a highly promising tumor immunotherapy target following PD-1/PD-L1. However, in the past two years, the development of related drugs has faced repeated setbacks.

Facing market concerns and doubts, Dr. Tian Wenzhi, founder of ImmunoMab, introduced the differentiated advantages of IMM01: "IMM01 is a SIRPα-Fc fusion protein. To address the safety issues of the CD47 molecule, IMM01 uses an engineered human SIRPα domain in the CD47 binding region. In vitro studies have shown that this domain does not bind to human red blood cells, offering significant safety advantages. Additionally, the company has applied deglycosylation modifications to this domain, reducing the molecule's immunogenicity. IMM01 fully activates macrophages through a dual mechanism of action—interfering with the CD47/SIRPα interaction to block the 'don't eat me' signal and activating the 'eat me' signal via Fcγ receptors on macrophages. Comparatively, IMM01 has an affinity KD of ~3nM, approximately one-thousandth that of Magrolimab. The moderate affinity allows IMM01 to maintain peripheral blood receptor occupancy at 10-15% (compared to over 90% for Magrolimab 14 days post-administration), thereby avoiding the common antigen-silencing effect seen with CD47 antibody drugs. The Phase II recommended dose of IMM01 is only 2.0mg/kg, whereas typical CD47 antibody doses range between 20 to 45mg/kg."

The advantages of Tidapacip are also confirmed in clinical data. Data from two Phase II clinical trials—IMM01 combined with azacitidine (AZA) for the treatment of previously untreated higher-risk myelodysplastic syndromes (HR-MDS), and IMM01 combined with tislelizumab for the treatment of classical Hodgkin lymphoma (cHL) after failure of prior PD-1 antibody therapy—were selected for oral presentation at the 2024 ASCO meeting. The excellent efficacy and safety data received enthusiastic responses at the conference. Among them, the oral presentation on IMM01 combined with tislelizumab for cHL after failure of prior PD-1 antibody therapy was awarded Best of ASCO in China® at the 2024 Annual Conference on Advances in Clinical Oncology in China (BOC).

According to ASCO data, in the treatment of previously untreated HR-MDS with IMM01 combined with azacitidine, among the total 51 evaluable patients, the complete response rate (CR) reached 33.3%, and the overall response rate (ORR) reached 64.7%; among the 34 patients treated for over 4 months, CR reached 50.0% and ORR reached 85.3%; among the 29 patients treated for over 6 months, CR reached 58.6% and ORR reached 89.7%. Responses improved continuously with prolonged treatment duration. The median observation time was 15.9 months; median progression-free survival (mPFS) and median overall survival (mOS) were not reached, with a 12-month OS of 71.1%. Additionally, significant recovery of overall hemoglobin (HGB) and platelet (PLT) levels was observed after IMM01 + AZA combination therapy, with a marked reduction in hemoglobin or platelet transfusions. IMM01 combined with AZA as a first-line treatment demonstrated good tolerability and significant efficacy in adult patients with higher-risk MDS.

IMM01 Combined with Tislelizumab in cHL Patients Who Failed Prior PD-1 Antibody Treatment: Phase II Trial Data Showed an ORR of 66.7% and a CR Rate of 24.2% in 33 Evaluable Patients (with an average of 4 prior treatment lines). A reduction in target lesion size was observed in 29 patients (87.9%). The median observation time was 6.87 months, the median time to response was 1.6 months, and the median progression-free survival and median duration of response were not reached. Overall safety and tolerability were good, with no cases of hemolysis observed.

02

Not Just CD47

As a fully self-developed innovative drug R&D platform company, an overview of ImiBio's product pipeline reveals not only CD47 and the recently out-licensed VEGF x PD-L1 and CTLA-4 ADCC+, but also innovative molecules targeting CD24, CD70, as well as ActRIIA, which shows great potential in the metabolism field, and related bispecific antibodies for this target. In the autoimmune field, which features relatively favorable competition dynamics and a vast market space, ImiBio’s Amulirafusp alfa (IMM0306, CD47 x CD20 mAb-Trap) has obtained IND approvals for two indications.

Yiming Angke's authorized partner this time, Instil Bio, is a clinical-stage biotech company focused on innovative cancer treatments. According to the company’s official website, its CEO, Bronson Crouch, is a seasoned entrepreneur and investor in the biopharmaceutical industry. Peloton Therapeutics, one of his investments, was acquired by Merck for an upfront payment of $1.1 billion in 2019; its core product, Belzutifan (PT2977), received FDA approval for marketing in 2023 to treat advanced renal cell carcinoma. Another immuno-oncology company, CoStim Pharmaceuticals, Inc., was acquired by Novartis in 2014, with the transaction amount undisclosed.

This BD collaboration will not only bring a substantial cash flow to ImmunoOnco but also accelerate its advancement in the larger market space of solid tumors.

(Source:瞪羚社)