Hello. Good evening. Good morning, everyone. Thank you for joining today's Zoom call on 2024. [Audio distortion]
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Hello? Hi. Sorry. I think someone was having the jacket. Thank you all. Good evening. Good morning. Thank you. My name is Sean Wu . It's my great honor to host this earnings conference call for Akeso. We're talking about 2024 annual results. Joining us today, the managing team includes the founder, Dr. Michelle Xia , Dr. Baiyong Li, CFO, Wang Bing, and the IR team. Today's call will be conducted in English, and it will be followed by Q&A. Without further ado, I'm going to pass over the call to Dr. Bing Wang .
Thank you very much, Sean. Thank you for hosting this conference for us. Welcome, everyone. I want to thank you all for joining Akeso on our 2024 earnings call. We look forward to going through some of the highlights of Akeso in 2024. First, this is a standard disclaimer page. We will be making some forward-looking statements here. Before we dive in on specific updates, we want to give you a highlight of the key accomplishments from 2024. First, on the R&D side, we achieved three new approvals, and we have five supplemental NDAs for new indications. Between our two cornerstone bispecifics, Ivonescimab and Cadonilimab, we have four positive phase III study readouts in 2024. In Cadonilimab, there are eight phase III studies across four major tumor types. For Ivonescimab, there are 12 phase III studies, including six phase IIIs.
That is in head-to-head versus PD-1 treatments across major tumor types. We also want to mention that we have the world's first CD47, our own Ligufalimab , that's in the first CD47 phase III study for a solid tumor indication in the world. In our early-stage pipelines, Akeso's first ADC entered phase I clinical studies. We also have our first bispecific ADC and our first bispecific autoimmune antibody that will enter clinical stage. On the commercial front, both of our cornerstone bispecific antibodies were included in the national reimbursement drug list in China. We have two metabolic and autoimmune candidates entering into commercial or near-commercial stage in 2024 as well. Our commercial team now covers over 1,000 members covering oncology and non-oncology indications. Financially, we have a very strong balance sheet. In 2024, we have RMB 2.1 billion in total revenues, and that includes RMB 2.0 billion in commercial sales.
We have RMB 7.3 billion in cash and cash equivalent on our balance sheet, and our annual operating loss is RMB 501 million, and our EBITDA loss is RMB 225 million. In the next few pages, we will go through some of these accomplishments in greater detail. The highlights of Akeso's pipeline development progress in 2024. In 2024, we had both of our first-in-class bispecific antibodies included in China's national reimbursement drug list. Cadonilimab was approved for reimbursement for second and third-line cervical cancer, and Ivonescimab was approved for EGFR TKI progressor non-small cell lung cancer. We also had three new drugs marketing authorizations approved by the CDE. Ivonescimab was approved, as we mentioned previously, for TKI progressor for non-small cell lung cancer. And also, Ebronucimab, our PCSK9 antibody, was approved for primary hypercholesterolemia as well as for heterozygous familial hypercholesterolemia.
In addition, Penpulimab, a PD-L1 antibody, was approved for third-line nasopharyngeal cancer. This is a molecule that we have outlicensed to Sino Biopharm . We also have two new supplemental NDAs for marketed drugs approved by the government, and that includes Cadonilimab for first-line gastric cancer as well as Penpulimab for second-line or greater nasopharyngeal carcinoma. We have five products submitted for NDA or supplemental NDA review, and this includes Cadonilimab for first-line cervical cancer, Ivonescimab for first-line PD-L1 positive non-small cell lung cancer, Penpulimab for first-line liver cancer, Ebdarokimab for psoriasis, and Gumokimab for psoriasis as well. Beyond our approvals and submissions, we also have 11 newly initiated phase III studies across six products. Most of these are focused on oncology and use either ivo or cado, or in combination with one of these two bispecifics.
For example, we have a phase III study that combines our CD47 antibody, Ligufalimab, with Ivonescimab, and a phase III study that combines our VEGFR2 receptor with Cadonilimab. We also have two immunology assets in phase III. Despite our late-stage success, our early-stage innovation continues. We have four new drug candidates entering IND and clinical stage in 2024, including our first bispecific ADC and our first bispecific autoimmune candidate. 2024 was a year of commercial growth and execution. In 2024, we achieved RMB 2 billion of commercial sales, a 25% growth from 2023. Our growth in volume is actually quite significant. However, in June of 2024, we proactively reduced the price of Cadonilimab by 54% as a key part of the plan for inclusion into the National Reimbursement Drug List in 2025.
This was a strategy that we had designed from the very beginning of the year, and the price cut was part of the strategy to increase adoption. The plan was a success, and cado was successfully included in the NRDL in January of 2025. On January 1st, 2025, oncologists in China prescribed the first treatment of Cadonilimab under the NRDL. Another key component of our commercial growth in 2024 was the approval of ivo, proposed EGFR TKI non-small cell lung cancer, in May of 2024. The approval happened on May 24th, and by May 31st, the first commercial batch of Ivonescimab was shipped. We were very successful in including ivo into the NRDL in January 2025, and like cado the first prescription for ivo under NRDL was written by oncologists in China on January 1st, 2025.
Our two core first-in-class bispecifics were included in NRDL from January 2025, as we highlighted in the last page. We want to emphasize that the core part of our commercial strategy in 2024 was to get both cado and ivo into the NRDL for 2025. This plan took almost the entire year to implement. However, it was a critical step in making sure that as many patients in China can benefit from these two lifesaving drugs as possible. The inclusion into the NRDL not only makes it eligible for reimbursement by insurance in China, but it can also expand the number of hospitals that can carry these two bispecific cancer therapies. In anticipation of the inclusion, we also added to our sales force. To lead our commercial effort, we recruited Dr. Kevin Guo as our new Chief Commercial Officer in the Q4 of 2024.
By the end of 2024, we cover over 1,000 hospitals across all provinces in China. With the inclusion into NRDL and under the leadership of Dr. Kevin Guo, our goal is to have 2,000 hospitals that can carry both cado and ivo by the end of 2025. Currently, Cadonilimab has been included in nearly 15 clinical treatment guidelines. These cover gynecological tumors, gastric cancer, liver cancer, esophageal cancer, and nasopharyngeal cancer. These are listed on the right side of the page. Cado is now widely covered in reimbursement by the NRDL, and we are actively engaging with insurers and other payers to expand coverage. We also have additional approved indications in the second-line cervical cancer and first-line gastric cancer. The NDA for the first-line, supplemental NDA for the first-line cervical cancer, is currently under review.
Without going through every item on the right side of the page, we want to highlight that these treatment guidelines for cado include recommendations for cervical, gastric, and some guidelines for liver cancer. The inclusion of cado in the clinical treatment guidelines and its approval is driven by its success in pivotal clinical studies in gastric and cervical cancers. Currently, Cadonilimab is approved for second and third-line cervical cancer as immunotherapy, first-line gastric cancer with chemo, and also first-line gastric cancer and chemo. The supplemental NDA for first-line cervical cancer with chemo is under final review. We're also enrolling cado in first-line PD-L1 negative non-small cell lung cancer, as well as consolidation therapy in unresectable, locally advanced non-small cell lung cancer. In liver cancer, we have finished enrollment for postoperative adjuvant therapy for liver cancer as immunotherapy.
We're also currently enrolling intermediate-stage liver cancer with Lenvatinib and transarterial chemoembolization or TACE, and the enrollment is ongoing. With Cadonilimab, there are a total of 28 clinical trials ongoing covering 20 indications. These include eight registrational or phase III clinical studies, three of which have obtained positive results. We're very excited about the global potential for our first and best-in-class PD-1 and CTLA-4 bispecific checkpoint antibody. In Ivonescimab, we see a molecule that combines a critical checkpoint mechanism and an anti-vascular mechanism to create the next generation of immunotherapy antibody. This combination, as well as our unique protein structure, provides a very broad spectrum of highly efficacious and low-toxicity anti-cancer agents. In total, ivo is included in 27-plus clinical studies covering 18 indications. These include 12 phase III clinical studies that are ongoing, of which we have positive results for two of these phase III studies.
There are three global clinical studies ongoing with ivo and six phase III studies that are head-to-head comparisons with approved or leading PD-1 antibody. There are additional multi-regional clinical trials in planning from our partner Summit to combine ivo with ADC from Pfizer, and some of these will commence in mid-2025. Currently, Ivonescimab is in seven phase III clinical studies and in particular lung cancer, two of which have received positive clinical results. According to Evaluate, the global market size for non-small cell lung cancer is over $25 billion a year in 2024. With all the clinical studies that we are running currently, we hope to tap into most of that market. We have already received approval for EGFR TKI progressor non-small cell lung cancer with chemo in May of 2024. First-line PD-1 positive non-small cell lung cancer is also currently under sNDA review.
It also was given a priority review. We also finished enrollment in a phase III study in first-line squamous cell non-small cell lung cancer plus chemo compared with Tislelizumab plus chemo. We are also planning a study in second-line PD-1 antibody resistant non-small cell lung cancer. In addition to the studies that we are running, our partner Summit Therapeutics is also running three phase III studies in lung cancer. The first one is a third-generation TKI progressor, EGFR TKI progressor non-small cell lung cancer chemo that is expected to have a data readout in mid-2025. Summit is also running two additional phase III studies that compare ivo, Pembro, and is enrolling globally at this time. Beyond lung cancer, Ivonescimab will also expand into additional solid tumor types. Five new phase III clinical studies targeting a broader market in multiple solid tumors are currently enrolling or about to be initiated.
Currently, we're enrolling phase III studies for ivo with chemo versus Tislelizumab with chemo in first-line biliary tract cancer. We're also enrolling a phase III study combining ivo with our own CD47 antibody, Ligufalimab, in first-line PD-1 positive head and neck cancer. We're also enrolling ivo plus chemo in first-line PD-1 negative triple negative breast cancer versus chemo. We have initiated ivo in phase III studies in first-line pancreatic cancer and first-line colorectal cancer. Additional studies for ivo in combination with ADC are in planning phase. Beyond the clinical study that Akeso is working on in ivo, the clinical studies that our partner Summit is doing in the U.S., there are also partnerships that expand Ivonescimab into new treatment combinations with antibody-drug conjugates and additional tumor types.
In February of 2025, Pfizer will partner with Summit to evaluate IVO in combination with Pfizer's ADC, and some of these studies will begin in mid-2025. Pfizer will be responsible for conducting the clinical operations, which will be jointly supervised between Pfizer and Summit. Akeso will be manufacturing all the supply of Ivonescimab for these studies. In addition, MD Anderson and Summit have also signed a five-year strategic collaboration to accelerate the development of Ivonescimab for multiple tumor types that include renal cell carcinoma, colorectal cancer, breast cancer, and glioblastoma. While the initial set of data and focus for Ivonescimab is in lung cancer, our efforts outside of lung cancer will meaningfully expand the market potential for Ivonescimab. One leading Wall Street biotech analyst at Goldman Sachs has estimated the global peak sales for Ivonescimab could reach $53 billion.
In this estimate, a significant contribution of potential sales will come from outside lung cancer in the mid-2030s. Another top-ranked analyst at Cantor Fitzgerald also recently published that the total potential market for the PD-1 and VEGF market can reach over $100 billion, or twice that of the current PD-1 market. We believe there are a lot of lessons to be learned from the launch of Keytruda by Merck and the competition for market share in the PD-1 market. Merck's strategic decision to be first-in-class and first-line non-small cell lung cancer, the biggest indication of PD-1 antibody, is a key reason why Pembrolizumab is a dominant market player in PD-1. In a similar vein, our significant lead in non-small cell lung cancer should also impart significant market share advantage for IVO in the global PD-1 VEGF market. We have a significant lead in other solid tumor types as well.
Beyond our approved IVO bispecific antibodies, we received approval in September 2024 for Ebronucimab, our PCSK9 antibody. It is approved for primary hypercholesterolemia and heterozygous familial hypercholesterolemia. Ebronucimab can provide a high potency reduction in LDL-C and can reduce cholesterol meaningfully in high-risk and very high-risk populations. It offers additional advantage in providing flexibility in dosing schedules for patients and facilitating compliance and has an excellent safety profile. Our most advanced autoimmune antibody that's Gumokimab, which targets IL-12 and IL-23, is in final review of its NDA for moderate to severe psoriasis. In our phase III data, we show rapid improvement in skin condition after two doses, and it has a long duration in the quality of life benefit for patients. Our second autoimmune antibody, which is under NDA review as well for moderate to severe plaque psoriasis, is Gumokimab, which targets IL-17.
Gumokimab has a rapid onset of action and provides clinically significant improvement after only two weeks of treatment. It is able to achieve a 90% skin lesion clearance at about 12 weeks and a 52-week period. We're also currently running a phase III study in ankylosing spondylitis. Manidiplimab is an IL-4R alpha that has finished enrollment for phase III studies for adult atopic dermatitis. We expect top-line readout in the second half of 2025. It is also currently enrolling in adolescent atopic dermatitis. We also recently filed an IND for a bispecific antibody that targets both IL-4R alpha and ST2 with intent to run studies for respiratory and dermatological indications here. Here we summarize our pipeline. Akeso's team has put quite a bit of thought and strategy into the targets that we design therapies around.
Besides the commercial and late-stage candidates that we just talked about, we also have a number of early-stage candidates in pre-IND and phase I studies. Many of these IO targets and bispecific IO targets. We have a total of five bispecific IO phase I studies. We also have a number of ADCs, such as our first-in-the-clinic study, ADC for HER3, and two bispecific ADCs. Our TROP2/Nectin-4 bispecific ADC is entering clinical stage, and we have an EGFR TROP2 bispecific ADC that is in pre-IND. In total, we have 16 potential first-in-class and best-in-class antibodies in the pipeline and 24 clinical stage candidates. This deep pipeline is a result of our continuing effort to innovate and to find therapeutic protein solutions for critical medical and med needs. Behind the commercial and pipeline candidates is our R&D production and commercial capabilities.
We have over 3,200 employees in total, with the largest portion, 1,100 in research and development. This is followed by over 1,000 people in commercial and marketing functions. Almost as big as our commercial R&D franchise is our manufacturing team at over 800 people. Our key sites are in the city of Zhongshan and Guangzhou, both based in the Guangdong Province in China. We are also in the process of opening a major R&D center in Shanghai. We have additional offices all around major centers in China, as well as clinical development capabilities in Australia and in the U.S. Our manufacturing follows best-in-class global standard manufacturing processes. Not only do we manufacture the therapeutic antibodies we develop and commercialize in China, we also manufacture all the clinical supplies for our partner Summit and their upcoming collaboration with Pfizer and ADC.
Most of this is based in the Guangdong Province in southern China. We currently have 94,000 liters capacity running, with plans to expand to 160,000 liters. Our clinical operations have continuously expanded since 2018. By the end of 2024, we have over 108 clinical studies ongoing, of which 20-plus are in phase III, where registration is ongoing. So far, in 2025, we are running over 120 clinical studies. All of this is driven by our internal pipeline. We also want to emphasize that our clinical operations team, as well as our CMC and manufacturing team, have worked in close alignment with our early-stage innovation team to ensure that this momentum and development flywheel continues on its current momentum. Here, we want to highlight our recent track record. All 10 candidates that have entered the clinic in 2019 have launched commercially. In NDA review, we're in phase III studies.
Some of these assets are out-licensed to collaborators. Drug development is hard, and perhaps there is an element of luck here, but our track record in the recent year has demonstrated consistent success. Here, we want to list the catalysts for 2025. I will not go through every item here. I will highlight a particular interest to some investors, maybe the phase III study for Ivonescimab with chemo in first-line squamous non-small cell lung cancer versus Tislelizumab plus chemo. We hope to have data for this study sometime this year. The other one is a global study for IVO for third-generation EGFR TKI progressors in non-small cell lung cancer. Our partner Summit have guided towards data in the middle of this year. In addition, we also have a number of phase III studies that will complete enrollment, as well as phase III initiation in both Cadonilimab and Ivonescimab.
On the early to mid-stage side, we'll have a number of bispecific IO candidates that may enter phase II in 2025, and a number of early-stage candidates in IO, ADC, and immunology that are entering into IND and phase I. Next, we want to focus on some data on our late-stage pipeline. One thing to mention is in 2024, we have over 80 publications in academic journals and conferences. First, in Cadonilimab. Previously, we have mentioned some of the clinical updates on the bottom, but our clinical results have been published in leading high-impact journals such as Lancet and Nature Medicine. This is a key validation of our development and clinical studies. In Cadonilimab, we have phase III studies in first-line gastric cancer that provide a meaningful survival benefit to all comers regardless of PD-1 expression.
Compassion 15, which is the name of the study, was invited by the AACR press as a key theme, as one of the four papers and a key theme for the conference. The result was also published in Nature Medicine. It is worth emphasizing that the survival benefit is meaningful even to those gastric cancer patients with low or negative PD-L1 expression. This is something that the current PD-1 treatments cannot provide. On September 26, 2024, the FDA had an ODAC meeting that reviewed the use of PD-1 antibodies for the treatment of gastric cancer. The panel of experts voted 10-2 and 11-1 to oppose the use of PD-1 treatments for PD-1 negative gastric cancer and gastroesophageal junction adenocarcinoma. Unlike Cadonilimab, they cannot provide benefits to patients that have negative or low expression in PD-L1.
The results of Compassion 15 and what posed at AACR are summarized here graphically. In all intensive treatment populations, Cadonilimab plus chemo provide a median overall survival of 15 months in comparison to 10.8 months for the placebo group. The outcome of this is a 38% reduction in the risk of death. In a group of patients that have CPS above 5, the risk of death is reduced by 44% for an OS hazard ratio of 0.56. For patients whose tumor has a CPS score below 5, the median OS is 14.81 compared to 11.11 for the control group, and the risk of death is decreased by 30%. We'll now look at the survival data for Cadonilimab in comparison to the leading PD-1 antibodies on the market.
Here, we compare Cadonilimab to Nivolumab, where the study was done in CheckMate 649, and Pembrolizumab, where the study was done in KEYNOTE-059 , as well as Tislelizumab and RATIONALE-305. On the bottom, we're able to compare the data for Nivo and Pembro graphically. In comparison, in comparison to the overall survival data for patients whose PD-L1 score and CPS below 10, you can clearly see the separation in the two lines for overall survival for Cadonilimab. There is a clear separation where for cad, the line is blue and the red line is for the control. The separation is clear at 12 months and widened further at 18 months. In contrast, in Nivo, the separation overall survival curve between the treatment and control arm is minimal. For Pembrolizumab, there's minimal separation at 11.7 months, the time for median OS, and a small separation in the later month.
If we look at patients whose PD-L1 score is CPS below 5, you can still clearly see the separation for the two lines for overall survival for Cadonilimab. There is a clear separation between the blue line for cado and the control for the red. The separation is clear at 12 months and widens further at 18 months as well. In contrast, for both Nivo and Pembro, the separation overall survival curve between the treatment arm and control arm is minimal. We look at the separation for the two curves for patients whose tumor are PD-L1 negative. In all cases, statistical significance has been reduced. However, in Cadonilimab, we can still see a clear separation between the test and the control arm for cado and a hazard ratio of 0.84.
In both Nivo and Pembro studies for PD-L1 negative patients, the overall survival curve has minimal separation and overlapping inserts in places. Lastly, we compare Cadonilimab with the other PD-1 in cases where the patient tumor expression has high PD-L1 expression or CPS greater than 10. Here, Cadonilimab shows a clear and widening OS curve separation as time progresses. Here, both Nivo and Pembro show a clear curve separation as well. Cadonilimab is able to provide an OS hazard ratio of 0.58. Nivo has a hazard ratio of 0.65 and Pembro 0.64. The past four slides highlight that Cadonilimab can provide a meaningful survival benefit for gastric patients in PD-L1 high, PD-L1 low, and PD-L1 negative patient populations, which is not the case for the other PD-1 on the market.
Similar to first-line gastric cancer, Cadonilimab is also able to provide a meaningful survival benefit in first-line cervical cancer in combination with chemo. Compassion 16 is the only phase III study in first-line cervical cancer that shows a survival benefit for patients with all levels of PD-L1 expression. Cadonilimab is able to provide a PFS hazard ratio of 0.62 and an OS hazard ratio of 0.64. The result was published in Lancet. More recently, we also published results of Compassion 18 at the annual meeting on women's cancer. We showed that Cadonilimab with concurrent chemoradiation therapy in locally advanced cervical cancer can provide 100% overall response rate and 84.8% complete response. This is the phase II data that we have published. In addition to our bispecific, in IO and chemoresistant gastric cancer, we also add our own VEGFR2 Pulocimab to Cadonilimab in a phase II study.
This is a very difficult-to-treat population, and we are able to achieve a 40% overall response rate and a 96% disease control rate. We're able to reach a median OS of 13.01 compared to 7.41 in previous studies. We're currently enrolling in a phase III trial in this combination. Our second bispecific, Ivonescimab, has also demonstrated significant clinical success. Besides the clinical achievement summarized on the bottom, we have also published our data in multiple leading conferences and high-impact journals. Our Harmony II data in first-line non-small cell lung cancer versus Pembrolizumab was first presented at a World Conference on Lung Cancer in September of 2024 and was recently published in The Lancet. At the 2024 ASCO, we published data from Harmony A, where we compared Ivonescimab plus chemo in EGFR TKI resistant non-squamous cell non-small cell lung cancer.
We showed a median PFS hazard ratio of 0.46 and a median OS hazard ratio of 0.8. One particularly important subgroup are patients with brain metastases at baseline. In this patient group, the PFS was 8.41, providing a PFS hazard ratio of 0.33. Just as importantly, the incidence of treatment-related adverse events was comparable to the control group. Our partner Summit is running a similar study in the U.S. called Harmony, and they have guided the top-line readout in mid-2025. Our next study for Ivonescimab is Harmony II, where we published our data at the 2024 WCLC conference in September in San Diego. This is a head-to-head study comparing ivo monotherapy with Pembrolizumab monotherapy. This study showed that Ivonescimab provided a median PFS of 11.14 months compared to 5.82 months for Pembrolizumab, resulting in a 0.51 hazard ratio.
Just as meaningful is that it showed clear benefits for both squamous and non-squamous subgroups. It also showed clear benefit in both PD-L1 low with a hazard ratio of 0.54 and PD-L1 high population with a hazard ratio of 0.46. The overall safety profile is also good, with no additional safety signal that was identified in the study. This result is the basis of our submission for a supplemental NDA to CDE in August of 2024, and it is currently under priority review. We have also finished enrollment for Harmony VI, which is our phase III study comparing ivo with chemo to Tislelizumab with chemo in first-line squamous cell non-small cell lung cancer. Phase II data shows an overall response rate of 71.4% and a PFS of 11.11 for squamous and an ORR of 54.2% and a median PFS of 13.31 for non-squamous. We expect data readout sometime in 2025.
Our partner Summit is running a similar global study called Harmony III, where they compare ivo plus chemo with Pembro plus chemo in first-line non-small cell lung cancer study. Harmony III includes both squamous and non-squamous cell in their study. We're also planning a phase III study for PD-L1 and PD-L1 resistant non-small cell lung cancer. Our phase II data shows an overall response rate of 40% and a median PFS of 7.11 in this very difficult-to-treat population. Phase III is currently in planning. Beyond lung cancer, we are currently enrolling in a phase III study for biliary tract cancer. Our phase II data, published in ASCO last year, shows a 63.3% ORR and a 100% disease control rate. For patients with gallbladder cancer, gallbladder cancer, the ORR is 77.8%. The median overall survival is 16.81 compared to 12.81 and 12.71 in previous studies with Nivolumab and Pembrolizumab.
The phase III trial enrollment is ongoing. In triple-negative breast cancer, we are currently enrolling in phase III for Ivonescimab. Our phase II data shows an ORR of 80% and a disease control rate of 100% for intensive treatment patient population. The median OS was not reached at the time of data cutoff. In patients with CPS below 10, the ORR was similar at 79.3%, and the disease control rate was also at 100%. In patients with CPS below 10, the median OS was not reached. The study shows very manageable safety profile, and the treatment related adverse effectively to death with continued voice and nothing. We have also initiated a phase III study in first-line colorectal cancer. This is based on our positive phase III data, where we showed an 81.8% ORR and a 100% disease control rate.
Again, safety was manageable and no treatment-related adverse effect has led to death or discontinuation. We also want to highlight the combination of our own CD47, Ligufalimab, in combination with Ivonescimab in head and neck cancer. We are currently enrolling in phase III. This is traditionally a very difficult-to-treat cancer, and at ESMO 2024, we showed that by adding Ligufalimab to Ivonescimab, we can double the ORR rate from 30% to 60%. The updated data shows an ORR of 65% and a disease control rate of 90% and with manageable safety profile. We're currently enrolling phase III for this study, and this will be a first phase III in solid tumor in the world that involves a CD47 antibody. Next, I will hand over to Akeso Chief Scientific Officer, Dr. Baiyong Li, to highlight our early-stage assets.
Our first lead ADC with the compound number AK13AD1.
This uses a tighter, stronger, more stable linker in serum and also has a unique CMC formulation. The goal with this novel design is to increase the safety profile and increase our therapeutic index for ADC. AK13AD1 has entered the clinical trial in Australia. We plan to combine with our bispecific antibody AK114 and AK112 shortly after. Our bispecific ADC, AK146D1, targets TROP2 and Nectin-4. TROP2 and Nectin-4 are targets that are strongly expressed in a number of tumor types. They have the characteristic co-expression profile in bladder, breast, head and neck, lung, and esophageal. We see this expression profile. AK146 has shown improved safety profile compared with TROP2 ADC and Nectin-4 ADC in our preclinical study. AK146D1, we have submitted IND and looking forward for clinical trial to initiate soon.
In the immune-related disease area, our bispecific antibody AK139, targeting IL-4R alpha and ST2, the IND has been filed in January. This compound is designed to target respiratory diseases like asthma and COPD, as well as dermatological diseases like atopic dermatitis. AK139 is the first-in-class bispecific antibody targeting these two targets. We designed the compound with this tetravalent structure and modified ST region to extend serum half-life and also improve safety profile. The compound is designed to capitalize on both the IL-4R alpha pathway and the ST2 alarmin pathway that are both critical for these allergy-related diseases. We have an antibody AK135 targeting IL-1R for chemotherapy-induced peripheral neuropathy. Chemo-induced peripheral neuropathy, CIPN, is a commonly occurring issue for patients receiving chemo treatment. A lot of these patients go on to develop chronic adverse effects. Pro-inflammatory cytokines are known to be critical factors driving the occurrence of CIPN.
IL-1RAP is a receptor that is common for a number of these critical cytokines. One antibody targeting IL-1RAP can block all of these different cytokines. An antibody in the clinic has provided initial proof of concept for targeting IL-1RAP for CIPN. Our compound, AK135, has received IND, and phase I dose escalation is ongoing.
Thank you, Dr. Li. The next session, we will go through the financial highlights for Akeso in 2024. Akeso's revenue in 2024 was RMB 2.12 billion. In 2024, the group's total commercial sales reached RMB 2.0 billion. This is increased by 25% from 2023 commercial sales of RMB 1.6 billion. The growth is primarily attributable to the commercialization of Ivonescimab, which was approved in May of 2024, and the increase in market adoption of Cadonilimab.
Collaboration income for the year ended December 31 amounted to RMB 122 million, primarily consisting of the upfront payment received from Summit Therapeutics for the amendment to the existing collaboration and license agreement between Akeso and Summit. This was announced in June of 2024. Gross profit. The group's gross profit for the year ending December 31, 2024, is RMB 1.835 billion. Excluding license and collaboration income, the gross profit of commercial sales for the period ended December 31, 2024, was RMB 1.71 billion, an increase of 16.5% from the gross profit from commercial sales of RMB 1.47 billion for the period ending December 31, 2023. Research and development expense was RMB 1.187 billion for the year ended December 31, 2024, a decrease of 5.3% from RMB 1.254 billion for the year ended December 31, 2023.
Despite expanding our clinical operation and the number of clinical studies, including multiple phase III, Akeso was able to reduce our R&D expense through the optimization of our in-house clinical team in recent years. Sales and marketing expenses. Sales and marketing expense was RMB 1.001 billion for the year ended December 31, 2024, an increase of 12.51% from RMB 890 million for the year ended December 31, 2023. The increase in sales and marketing expense was primarily driven by expanded commercial activities for Cadonilimab, which expanded approval to include first-line gastric cancer in September of 2024, and Ivonescimab, which was approved and commercially launched in May of 2024. Administrative expense was RMB 204 million for the year ended December 31, 2024, an increase of 1.4% from RMB 200 million in the year ended December 31, 2023.
The loss for the year was RMB 501 million for the year ended December 31, 2024, compared to a profit of RMB 1.942 billion for the year ended December 31, 2023. The profit for 2023 is mainly due to the initial agreement that Akeso has signed with our collaboration partner, Summit for Ivonescimab. Excluding license income, the adjusted operating loss for 2024 was a loss of RMB 657 million, a decrease of 16.6% from 2023, which had an adjusted operating loss of RMB 788 million. We also want to highlight that we have a very strong balance sheet. In 2024, we did equity raises in March and October of the year, raising a total of RMB 2.8 billion in cash. Our cash and cash equivalent as of December 31, 2024, is RMB 7.3 billion. Our EBITDA for 2024 is a loss of RMB 225 million.
The cash we have on hand enables us to continue to invest in our highly productive clinical studies, our state-of-the-art manufacturing, and to continue to grow our commercial capabilities. Reduction in operating loss in 2024. Our commercial operations have continued to steadily improve. On the chart on the left, it shows that we have steadily grown our product sales over the last three years. Cadonilimab was first shipped in July of 2022, and in 2023, by 2023, we show continuous market uptake for market-related bispecific. When you consider that we had a 53% price cut in Cadonilimab in June of 2024, the revenue growth does not fully take into account the increase in the number of patients that benefit from Cadonilimab. On the expense side, we've been able to control the main expense item in our operating expense.
The chart in the middle summarizes the expense trend, R&D, sales and marketing expense, and administrative expense. The R&D expense has shown a slight decrease in the last two years despite an expanded clinical effort. The sales and marketing expense has been growing slower than our commercial sales, with the margins decreasing from over 55% of commercial sales in 2023 to 50% of commercial sales in 2024. General administrative expense has also improved by less than 2% from 2023 to 2024. The resulting benefit of expense control with continuous growth in commercial sales has resulted in our decreasing loss year by year on an adjusted basis. That concludes the finance section of our report. Before we go into Q&A, we also want to highlight some key points from 2024. First, we want to mention that Akeso has two of the leading bispecific IO agents in the world.
We have demonstrated commercial leadership in bispecific IO in China in 2024, and we expect to expand on our success globally for both of these molecules in the coming years. Ivonescimab is the world's best-in-class IO therapy for the treatment of lung cancer and expected to be a standard of care for many types of lung cancer treatment in the near future. We're also expanding this to a number of additional indications in late-stage studies. Cadonilimab is currently approved for two indications in China, and we expect to expand on this to have liver and lung that is beta-1 negative in the next few years. It is highly differentiated in a safety profile and durable OS for many patients that have used it.
Akeso's deep pipeline of internally developed antibodies, including other bispecific IOs and bispecific ADC, enabled us to create a broad set of cancer combination therapy using wholly owned assets. Our world-class CMC and manufacturing creates a dependable and cost-competitive stream of therapeutic products for patients in China and around the world. All of the clinical data and the manufacturing data supports a growing commercial franchise. Both of our bispecific have entered into the National Reimbursement Drug List in 2025, and we are excited about the commercial potential for market-leading Cadonilimab and Ivonescimab. Lastly, and most importantly, we want to thank our investors for their strong support of Akeso over the years. None of this is possible without you. With that, we conclude our presentation. Sean, back to you. Okay.
Thank you, Bing. Yeah, thank you, Dr. Baiyong Li. Thank you, Ben, for your very comprehensive presentation.
Congratulations again on another great year of achievement, and also you saw two kind of key bispecific drugs getting into the reimbursement list. My first, I'll ask you the first question. My question would be related to the performance of your two products after getting into the reimbursement list. I mean, three months have passed. How are things shaping up? And do you did see greater kind of some kind of scaling effect of sales marketing? How do you see your sales expenses proportion of sales marketing as a proportion of sales going forward?
Hey, Sean, we're not going to provide guidance for 2025. I think Michelle has also highlighted in the Chinese portion of our presentation earlier today is that, first of all, we went through a major price cut to get into NRDL.
We're also in the process of entering a lot more hospitals because of this access. It's really hard to give very clear guidelines for the sales. As she highlighted earlier today, we're shipping a lot of volume out the door on a weekly basis. That's all we can say for now.
Okay. That's a very good note. I guess as a Chief Executive on the front line, I meet people a lot. People have been talking a lot about new measures from the Chinese government that may support developmental innovation in China. What's the experience from Dr. Xia and Dr. Li about the new policies? How do you think this will impact the industry and your company? Just very quickly for the sake of time.
If I could take a first stab at the question, Sean, I think what you're asking is, what is the Chinese government's policy towards biotech innovation, and how does that affect us? Is that what you're saying?
I'm saying there are some new rumors, new measures being proposed. I'd like to say as the leading biotech, how Dr. Xia, like she thinks, evolve, how beneficial that could be to industry and specifically for Akeso.
Yeah. Sean, I'm sorry. Maybe it's the quality of sound. I'm having trouble answering.
Oh, that's okay. I think I'll just leave this to ask about time. Maybe next question, let's ask Tracy to raise her question for sake of time.
Thank you.
Yeah. Thanks, Sean. And many thanks to Michelle, Bing, and Dr. Li and other management team for taking my question. First of all, congrats on the remarkable achievements and progress over the past year. I would like to follow up on Dr. Baiyong Li's presentation on Akeso's ADC platform. We are very delighted to see that two candidates are already in the clinical stage. Can we have your comments to share with us Akeso's unique advantages and also the competitive positioning compared to other industry leaders, especially on the bispecific ADC side? Also, will Akeso plan to quickly expand your pipeline through internal IND or external partnerships? Thank you.
Thank you for the question. ADC, of course, shows great potential right now. In many occasions, especially late lines right now, show spectacular results and go into early lines. Everyone has seen the issue with ADC right now. It is great efficacy, but also unavoidable toxicity, right?
The therapeutic index for ADC is very poor, I have to say, right? You do a lot of, yeah, you have to spend a lot of effort really titrating the dose in order to find the dose of ADC that's barely acceptable in the clinic. You can increase your dose to achieve better efficacy, but your toxicity also increases along with it. How to solve the toxicity issue is really the key question for everyone in the field. We as well, right? We are a relatively late comer. We are really focusing on how do we lower tox and improve the therapeutic index. As mentioned, we try to use a number of approaches to achieve that. Whether we achieve that is a question that we have to wait till we have results from the clinic.
Akeso's advantage, I think right now, we have already bispecific that's well planted that we can combine with to expand into the already achieved efficacy in a number of diseases, and we can add on to our ADC quickly to capture more ground for us. I think that's our advantage. Maybe Michelle, you can add a few words.
Yes. Yeah, on top of your, that was a very good point. I guess one thing is that if we can make a good ADC molecule, right? And Baiyong mentioned about ADC molecule, whether we can again further reduce toxicity and therefore increase therapeutic window, that's by ADC alone, we're talking about can you make a better molecule. And that part, our internal R&D team definitely made the best effort we can to answer this question from a preclinical point of view.
Now we moved our molecules forward to clinical stage. We will see until we find the clinical results. On top of that, I guess currently we have our two cornerstone bispecific IO products. That really added an advantage of our combination strategy, IO plus ADC. You know, recently I talked to doctors from hospitals. A lot of them mentioned about the future clinical advancement. If you have an IO plus ADC, that will be a very best combination. I agree with that. I think from that point of view, with the good clinical results from our year 2024 results, we can see that we really established the next generation of IO products beyond the PD-1 or PD-L1 alone molecule. Therefore, IO products, we already kind of evolution, I mean, from the first generation PD-1 or PD-L1, PD-1 or PD-L1 mono target antibody moved to bispecific.
This is one part of the combination. Another part of the combination, either if we can get a better safety molecule or we can have our bispecific ADC works. This combination put together, bispecific antibody and bispecific ADC, that maybe really put us, although it's going to be later than others, but maybe a better, maybe actually not late strategy for us to work on that. I think that's definitely an advantage. Our partner Summit already made a very good deal with Pfizer. Pfizer has a series of the ADC molecules in their hand. You can see that the deal between Summit and Pfizer, the deal itself actually gives the opportunity that Ivonescimab will combine all the ADC pipelines from Pfizer. From that point of view, that will also give us the various possibility to test the combination as much as possible.
Yeah, I think we are in a good position for that part of the process.
That is great to know. Thank you. Thank you so much, Michelle. And thank you to Dr. Li as well. Thank you.
Is there any other?
Nope. Yeah. Sean, do we have time for one more question, or are we out of time?
I think we are clear out of time, but I think we can ask a bit of a question. I would say, as far as now, the Summit is gaining a lot of recognition, just like you mentioned, the $52 is focused for PTs based on someone's coverage of Summit. Of course, we would like to say, how is your collaboration with Summit? Clearly, you guys are working together very well.
You kind of for new things, how do you think going forward? I guess you must be quite bullish about all those recognitions. Now things are moving along, so we should see quite a lot of catalysts this year, right?
Yeah. Thank you, Sean, for the question. No, I think our collaboration Summit is fantastic. They are a very good partner. I think we have a very good relationship at all levels, whether it's clinical development, whether it's manufacturing and CMC. We cannot ask for a better partner in Summit. They've been very supportive. We're obviously a major shareholder in Summit, so we're very much rooting for each other's success. Bob and Maky are two of our biggest cheerleaders, and we really appreciate having them as partners in the U.S. and actually for the rest of the world. We cannot ask for a better partner in the Summit.
Thank you very much. We are running out of time. Does management have any conclusion remarks?
No, I think we're good. Thank you, Sean, for giving us the opportunity to share and for Morgan Stanley for hosting our 2024 earnings call in English. We appreciate all the support from our investors and from everybody else in the community. We look forward to giving you, I guess, our next update in August and tell them, "Thank you very much."
Thank you.
Thank you very much. Thank you. We are looking forward to another great year from you. Thank you. Bye. Thanks.