2022 AACR summary: 10 products from 7 major tracks, the domestic innovative drug "beautiful boy" is coming

With the closing of the 2022 AACR, the new drug data or research progress of domestic innovative pharmaceutical companies has also been unveiled

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At the 2022 AACR meeting, Qilu Pharma announced the preclinical data of the fourth-generation EGFR inhibitor QLH11811

It is not difficult to speculate that QLH11811 will also cover a variety of clinical drug use scenarios

In addition, Hongyun Bio also announced the preclinical data of the fourth-generation EGFR inhibitor H002 with clinical approval at the AACR meeting

The preclinical data of H002 is also excellent, and it also covers a combination of multiple drug resistance mutations, and has both first-line and second-line drug potential

NO.

In 2022 AACR, Yifang Bio announced the early data of the clinical I study of the KRAS G12C inhibitor D-1553, which also made D-1553 the first domestic KRAS inhibitor to publish clinical data

The data showed that at the PR2D dose, D-1553 achieved an ORR of 40.

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In China, Shenghe Pharmaceutical has started clinical research on related drugs, and Simcere and CSPC have also obtained clinical licenses respectively

The data show that SCR-6277 has the potential for intratumor specific distribution, the intratumor drug concentration to plasma drug concentration ratio (T/P) is significantly better than that of GSK3326595, and it shows growth inhibition on tumor cells or grafts such as CLL (Z-138)

In addition to PRMT5, Simcere also announced the preclinical data of MAT2A inhibitor SCR-7952, RAD51 inhibitor SCR-6992 and CDK2/4/6 inhibitor SCR-8079 at the conference

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4 BTK not far behind

Bruton's tyrosine kinase (BTK) is an important signaling molecule in the B cell receptor pathway.
It is expressed in various developmental stages of B cells and participates in the regulation of B cell proliferation, differentiation and apoptosis.
It has become a field of tumor therapy and immune diseases.
The target that has attracted much attention is also a typical representative of China's innovative drugs going overseas
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With the clinical application of non-covalent inhibitors, the C481S mutation has become a common known resistance mechanism for such products
.
Merck and Eli Lilly took the lead in the layout, and domestic companies are naturally not far behind
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Similar products of Chi-Med Pharmaceuticals and Yehui Pharmaceuticals have started clinical research, and Haibowei Pharmaceutical has also completed the IND application
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In 2022 AACR, Fuchuang Pharma announced the preclinical data of BTK C481S inhibitor FCN-589
.
Compared to ARQ531, FCN-589 was able to achieve higher tumor growth inhibition at similar or lower dose levels
.

In addition, pirtobrutinib made another appearance in the AACR, continuing to demonstrate strong tumor inhibition and clinical potential
.

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5 PD-L1 adds another small molecule player

Immunotherapy represented by PD-1/L1 significantly prolongs the survival of tumor responders, especially in the field of lung cancer, and has become the new standard therapy
.
However, in the field of PD-1/L1, only antibody drugs are currently on the market, and small molecule PD-1/L1 is still in the clinical exploration stage
.

In 2022 AACR, Ascletis Pharma, Heyu Pharma and Betta Pharmaceuticals respectively brought preclinical data on PD-L1 small molecule drugs under clinical development
.
ASC61 is a PD-L1 small molecule drug developed by Ascletis Pharma.
Preclinical in vivo data show that ASC61 can achieve similar performance to atezolizumab (5mg/kg) at a dose of 100mg/kg.
tumor suppressor effect
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Heyu Medicine's ABSK043 mainly carried out the in vivo efficacy comparison with chemotherapy drugs, while Betta's BPI-371153 carried out the in vivo efficacy comparison with durvalumab
.
Relative to durvalumab (10 mg/kg), BPI-371153 showed similar tumor inhibition at a dose of 100 mg/kg
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Small-molecule drugs are considered to be able to penetrate tumor tissues, especially to kill tumor cells far away from blood vessels.
Coupled with many advantages such as convenient oral administration, they are also considered to be a potential track
.
However, the final efficacy and whether the replacement of antibody drugs can be achieved remains to be clinically verified
.

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6 PI3K Nirvana Rebirth

At the end of 2021, due to the withdrawal wave of AA indications opened by PI3K inhibitors, duensib was the first to withdraw from relapsed and refractory follicular lymphoma (FL)
.
In 2022, other PI3K listed drugs will also be subject to withdrawal of indications or investigation
.
Gilead announced the withdrawal of two indications of FL and SLL in the US market, the FDA opened a safety investigation of eblixide, Bayer withdrew the listing application of MZL in the EU, Incyte withdrew the listing application of FL, MZL and MCL from the FDA and MEI Pharma was required by the FDA to add new clinical studies to submit a marketing application
.
It can be said that PI3K inhibitors in the field of hematological tumors, whether they have options or not, have not been spared in this round of shocks, which are reflected by the concerns of regulatory agencies about the efficacy or safety of such drugs
.

In China, through authorized introduction and independent research and development, a huge pipeline of PI3K products has also been established, and the number of active PI3K clinical products has reached 25 (excluding MNC, including IND)
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In 2022 AACR, Hexion Pharmaceuticals, Chi-Med Pharmaceuticals, Zhengxiang Pharmaceuticals, and Fuchuang Pharmaceuticals also made appearances with related products
.
Among them, Hexion announced the clinical data of the selective PI3Kα inhibitor HS-10352 in breast cancer research
.

Preliminary results show that HS-10352 has an acceptable safety potential with a maximum tolerated dose of 6 mg QD
.
The most common (≥ 30%) treatment-related adverse events (TRAEs) were hyperglycemia (88.
9%, n=16), weight loss (61.
1%, n=11), increased insulin C-peptide, and diarrhea (33.
3% each, n=11).
n=6)
.
Grade 3-4 TRAEs included hyperglycemia (8 mg, n=2), weight loss (6 mg, n=2), fatigue (8 mg, n=1), blurred vision (8 mg, n=1), high Kalemia (8 mg, n=1) and hypocalcemia (8 mg, n=1)
.
The overall response rate and disease control rate of all patients (n=18) were 27.
8% and 55.
6%, respectively.
In 6 patients with PIK3CA mutation, the ORR was 50.
0% (3 patients with 6 mg PR) and the DCR was 100.
0% (6 mg, n=4; 8 mg, n=2)
.
At the tolerated dose (6 mg), the ORR of 4 patients with PIK3CA mutations reached 75.
0%
.

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7 CCR8 new opportunities are coming

CCR8 is specifically highly expressed on tumor-infiltrating regulatory T cells (Treg), while the level of CCR8+ Treg cells in blood and normal tissues is low.
Targeting CCR8 may be more selective than other methods of eliminating Treg
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At the same time, CCR8 is also an opportunity target of this AACR new drug development screened by the medical cube
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At the 2022 AACR, Jiahe Biotech and Zai Lab all disclosed preclinical data on CCR8 antibody drugs at the meeting
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GB2101 is a CCR8 antibody drug produced by Chia Bio through hybridomas.
In vitro and in vivo research data show that GB2101 shows effective binding to CCR8-expressing cells, and can effectively block CCL1 binding and CCL1-induced signals
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Furthermore, the afucosylation modification of GB2101 improved the ADCC response and exhibited ADCC activity against target cells
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GB2101 has initially shown inhibitory effect on tumor growth in syngeneic xenograft models, and its clinical potential remains to be further verified
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ZL-1218 is a humanized therapeutic antibody developed by Zai Lab, which binds to human CCR8 with high affinity and specificity, and can induce potent ADCC activity, thereby achieving strong NK cell-mediated anti-CCR8-expressing Tregs kill
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Disclosed preclinical data show that in a syngeneic tumor-bearing human CCR8 knock-in mouse model, ZL-1218 reduces intratumoral Treg cells to significantly inhibit tumor growth in a dose-dependent manner, especially in response to PD-1 antibody When used in combination, enhanced significant antitumor activity is achieved
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There are more and more international voices on Chinese innovative drugs.
In addition to the above 10 products in the 7 major tracks, this AACR still has many innovative drugs from Chinese pharmaceutical companies appearing, including various ADC drugs, a variety of differentiated double-antibody drugs or Cell therapy, etc.
, will not be listed one by one due to space limitations
.
For this AACR, if there are research progress or interesting report content that deserves special attention, you may also leave a message for discussion
.